AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2690-4861/307
Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
*Corresponding Author: Yu Liu, Department of Thoracic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, PR China.
Citation: Zhang W., Zhu W., Xu S., Liu Y., (2023), Establishment and Validation of Prognostic Model of Lung Adenocarcinoma Based on Apoptosis-Related Genes, International Journal of Clinical Case Reports and Reviews, 13(5); DOI: 10.31579/2690-4861/307
Copyright: © 2023, Yu Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 10 April 2023 | Accepted: 25 April 2023 | Published: 02 May 2023
Keywords: apoptosis; lung adenocarcinoma; prognosis; risk model; biology message
Objective: Apoptosis is an autonomous cell death process controlled by genes that can keep the internal environment of cells relatively stable. Lately, many studies have shown that apoptosis plays an important role in the construction of tumor microenvironment, mainly through the release of a series of regulatory factors to control cell growth. Therefore, it is very valuable to find and explore the possible role of apoptosis in the pathogenesis of lung cancer and its impact on the prognosis of patients.
Materials and Methods: We selected 10 apoptosis-related genes and used different statistical methods to construct a model to predict the survival and prognosis of patients with lung adenocarcinoma. Univariate and multivariate Cox analysis were used to evaluate the predictive power and value of prognostic models, as well as receiver operating characteristic (ROC) curve analysis.
Results: We defined two subgroups (cluster1 and cluster2). Compared with cluster1, cluster2 was named "apoptosis inhibition subgroup". The survival prognosis of cluster1 was significantly better than that of cluster2, and the infiltration of immune cells in cluster2 suggested that its immune system was inhibited. Then, we established a new prognostic model of apoptosis-related genes to identify high-risk patients with lung adenocarcinoma. Two types of Cox proportional hazards analysis and ROC curve showed that our model can be used as a new independent factor for the prognosis of lung adenocarcinoma patients, and had strong predictive ability.
Conclusion: Apoptosis is involved in the formation and development of lung adenocarcinoma and plays an important role. Our survival model can better predict the survival and prognosis of lung adenocarcinoma, and our study may be helpful for further research on new therapeutic targets and precise individualized treatment in the future.
Lung cancer is a malignant tumor with high incidence rate and high mortality in worldwide[1, 2]. The incidence rate of non-small cell lung cancer (NSCLC) accounts for about 85% of the total incidence of lung cancer, and lung adenocarcinoma (LUAD) accounts for 40% [3]. Although considerable progress has been made in exploring lung cancer biology and multimodal treatment, prognosis of lung cancer patients is still far from satisfactory. This is partly because the current guided staging method could not accurately predict the prognosis of lung cancer. The reason why some patients with early lung cancer relapse or metastasize is that they do not receive effective adjuvant therapy after operation [4, 5]. Through some current diagnostic methods, such as computed tomography, about 40% of lung cancer patients are still diagnosed with distant metastasis [6]. Therefore, finding reliable predictors of prognosis will bring great value to guide the treatment of LUAD [7].
Apoptosis is a special biological process, which leads to pathological changes different from necrosis by activating an evolutionarily conserved intracellular pathway, and finally leads to programmed cell death. Apoptosis involves several biological and pathological processes, such as embryonic development, steady-state maintenance of tissues and organs, tumorigenesis and tumor progression [8, 9]. At present, the existing research shows that apoptosis is involved in the process of tumor occurrence and development, and has an important impact on tumor treatment [10]. As one of the characteristics of cancer, acquired resistance to apoptotic cell death is mainly due to the overexpression of anti-apoptotic genes and the down-regulation or mutation of Pro apoptotic related genes [11]. At present, there is no method based on apoptosis-related genes expression to identify high-risk patients with LUAD.
This study screened hallmark gene sets enriched in the apoptotic pathway from the Molecular Signatures Database（http://www.gsea-msigdb.org/gsea/index.jsp），and constructed the co-expression network of apoptosis-related genes in LUAD. Using Cox analysis, we selected the expression characteristics of the first 21 apoptosis-related genes with HR significance to characterize the different apoptosis states of LUAD samples, and identified apoptosis status in the characteristics of LUAD patients as the main risk factor for overall survival. Then we studied an independent cohort to verify its prognostic value. In addition, this paper also describes the infiltration of 22 immune cell types in LUAD, the clinical characteristics of patients, and their correlation with the different expression of apoptosis-related genes. These results are helpful to further prove that our model has better prognostic ability, and to further explore and reveal the mechanism of apoptosis in the development of LUAD.
Source of sample data
In our study, the gene expression data and clinical data of lung cancer patients were collected from The Cancer Genome Atlas (TCGA) database (https://tcga-data.nci.nih.gov/tcga/). After excluding patients with repeated and missing clinical information, we analyzed the data of the remaining 494 patients. Among them, 248 patient data were used as the training set, the remaining 246 patient data were used as the validation set. Through the different analysis, there was no significant difference in age, gender, stage and other clinical characteristics between the two groups (Table 1). All gene expression data in this study were standardized, and we only used open-access data, which meets the requirements of ethical review.
Table 1: There was no significant difference in clinical characteristics between training set and validation set.
Screening and obtaining of apoptosis-related genes
A list of transcriptome profiling data of apoptosis-related gene and hallmark gene sets was obtained from the Molecular Signatures Database (MSigDB) (http://www.gsea-msigdb.org/gsea/index.jsp). A total of 1434 apoptosis-related genes were screened out, and finally we obtained 21 the most significant genes through Cox analysis.
Correlation between immune characterization and apoptosis
We obtained data on 22 immune cells, including T cells CD8, T cells CD4 naive, T cells CD4 memory activated, T cells CD4 memory resting, T cells follicular helper, T cells regulatory (Tregs), T cells gamma delta, B cells naive, B cells memory, Monocytes, NK cells resting, NK cells activated, Plasma cells, Macrophages M0, Macrophages M1, Macrophages M2, Dendritic cells resting, Dendritic cells activated, Mast cells resting, Mast cells activated, Eosinophils and Neutrophils. All data are downloaded from the ImmuCellAI database. We used limma software package to analyze the relationship between the infiltration of these immune cells and the expression level of apoptotic-related genes. And then we assessed the infiltration difference of them.
Identification of apoptosis-related genes prognostic signatures for LUAD
We identified 21 apoptosis-related genes by using univariate Cox proportional hazard analysis. After that, the least absolute shrinkage and selection operator (LASSO) Cox regression model was used to further screen for the best prognostic markers with P<0>
Risk score = coef (gene1) × expr (gene1) +
coef (gene2) × expr (gene2) +
……
coef (gene n) × expr (gene n).
coef (gene n) is the coefficient of each gene.
Expr (gene n) is defined as the expression of apoptosis-related genes.
n represents the number of apoptosis-related genes selected in our model.
It means that the gene plays a protective role when the coefficient of gene is less than 0, and if it is greater than 0, it means that the prognosis of patients will become worse. According to the median risk score, we divided the patients into two groups: high-risk and low-risk group, and evaluated the difference between them. Then we used the survival ROC R package to assess the accuracy of the prediction function of the model. In addition, we also evaluated the relationship between risk score (RS) and clinical factors.
Results
Consensus Clustering Showed Different expression of apoptosis related-genes in the Two LUAD Gene Clusters
A total of 1434 apoptosis-related genes were showed in the Molecular Signatures Database (MSigDB), and the PPI network is shown as Figure 1A. Then we screened and analyzed the expression characteristics of a group of related genes highly enriched in apoptosis related pathways. In order to understand their role in LUAD, we studied the differences of these biological signals in tumor tissues and normal tissues, and found that many genes expressed abnormally in the LUAD samples, as shown as Figure 1B. And we selected 21 genes including 4 down-regulated and 17 up-regulated genes with significant differences (Figure 1C).
Figure 1: 21 genes were found to be significantly associated with apoptosis.
Then, we used the Consensus Clustering Method to cluster 494 TCGA LUAD tumor samples to determine their apoptotic status. The result demonstrated that when the value of K is 2, the interference between subgroups is smaller than that in other cases (Figure 2A). Therefore, we finally identified them as two subgroups, namely cluster1 (n=416) and cluster2 (n=78). We compared the transcriptional profiles between cluster1 and cluster2 by principal component analysis, and found that there were significant differences between two subgroups (Figure 2B). The expression level of apoptosis-related genes was higher in cluster1, but lower in cluster2, so we defined the cluster2 as “apoptosis inhibition subgroup” compared with cluster1. Through Kaplan-Meier survival analysis, we found that cluster1 with high expression of apoptosis-related genes has better overall survival (OS) than cluster, P < 0>Figure 2C).
Immune Cells Infiltration of Different apoptosis-related gene expression in LUAD
Some evidence suggested that immune cells infiltration of tumor was associated to clinical response of treatment and cancer prognosis, including LUAD. Therefore, we analyzed 22 kinds of immune cells in LUAD, including 7 T-cell subtypes, 2 B-cell subtypes and Monocytes, NK cells resting, NK cells activated, Plasma cells, Macrophages M0, Macrophages M1, Macrophages M2, Dendritic cells resting, Dendritic cells activated, Mast cells resting, Mast cells activated, Eosinophils and Neutrophils. Figure 2D shows the different infiltration of immune cells in the two subgroups.
Apparently, the Dendritic cells and Mast cells that may play a promoting role in killing tumor cells in cluster2 have less infiltration, while Tregs and macrophages are more, while cluster1 shows the opposite trend. The results showed that the immune system in cluster2 were inhibited, which predicted the poor survival prognosis (Figure 2E).
Figure 2: Consensus Clustering identified two clusters of LUAD with different apoptosis status.
Establishment of prognostic model of apoptosis-related genes
In order to find prognostic indicators related to apoptosis, we performed Cox regression analysis on different gene expression and overall survival (OS) data of 248 LUAD samples. The results showed that 21 genes were significantly associated with OS, of which 17 genes were highly expressed and the other 4 genes were low expressed. The results of lasso Cox regression analysis (Figure 3A, B) showed that 9 up-regulated genes (DNM1L, SOD1, TGFB2, BIRC3, KRT18, BIK, DNAJA1, TIMP1, BCL2L10) and one down-regulated gene (CYLD) may be the most powerful prognostic markers.
Figure 3: Establishment of apoptosis related gene markers.
(A, B) Lasso Cox regression was used to construct effective prognostic markers.
The coefficients of 10 genes are shown in Table 2. We used Lasso analysis to calculate the coefficient of each marker to obtain the risk score calculation formula, as shown below: risk score = 0.005534 * expr (DNM1L) + 0.001061 * expr (SOD1) + 0.031586 * expr (TGFB2) + 0.008554 * expr (BIRC3) + 0.000488 * expr (KRT18) + 0.004843 * expr (BIK) + 0.002794 * expr (DNAJA1) + 0.000655 * expr (TIMP1) + 0.056489 * expr (BCL2L10) + (-0.054429) * expr (CYLD). All samples were scored by the above formula and divided into high-risk group and low-risk group according to the median. And the results of Kaplan-Meier analysis showed that compared with the low-risk group, the prognosis of the high-risk group was significantly worse (Figure 4A).
Then, we evaluated the model and survival status of LUAD patients and visualized them by using risk curve and scatter plot (Figure 4B-D). This indicated that the occurrence of mortality depends on the risk score. The heatmap of these 10 apoptosis-related genes showed, 9 genes (DNM1L, SOD1, TGFB2, BIRC3, KRT18, BIK, DNAJA1, TIMP1, BCL2L10) were highly expressed in high-risk group, while CYLD was highly expressed in low-risk group.
Figure 4: Establishment of prognostic risk scoring model.
Evaluation and Validation of the survival model for LUAD patients
We performed univariate and multivariate Cox regression analysis to evaluate whether the survival model of these 10 apoptosis-related genes can be used as independent prognostic factors of LUAD. In univariate Cox regression analysis, we found that tumor stage was related to OS, as well as risk score. The hazard ratio (HR) of risk score was 1.363(95% CI 1.229-1.511) (P < 0>Figure 5A, B).
The area under ROC (AUC) curve was used in TCGA train set and test set to evaluate the sensitivity and specificity of the risk scoring model in 1-, 3- and 5-year prediction. We calculated the area under the ROC curve of the risk score, and the results showed that the model has a good effect in predicting the prognosis (Figure 5C).
We calculated the risk score from 246 samples in the test set and validated our model. Based on the above formula and the best dividing point, we calculated the risk score of each sample and divided these patients into high-risk group (n=122) and low-risk group (n=124). It should be noted that, consistent with the results of the train set samples, the prognosis of the high-risk group was significantly worse in the test set (P < 0>Figure 4E). The risk curve, scatter diagram and heatmap in the validation set also showed the same results as the train set (Figure 4F-H). Then, we performed univariate and multivariate Cox regression analysis on the validation set, and the results showed that the risk score can still be used as an independent prognostic factor for patients with LUAD (Figure 5D, E). The AUC values of 1-, 3- and 5-year prognosis also proved good predictive ability (Figure 5F). And the AUC value of the total sample also proves this result again (Figure 5G).
Figure 5: ROC and Cox analysis of risk characteristics based on 10 Characteristic Genes.
(A, B) Univariate Cox regression analysis and multivariate Cox regression analysis in the train set demonstrated that Risk Score was an independent risk factor for OS.
(C) ROC analysis of overall survival for the 10-gene signature in train cohort.
(D, E) Univariate Cox regression analysis and multivariate Cox regression analysis in the train set.
(F) ROC analysis of overall survival in the test set.
(G) Total ROC curve of train set and test set samples.
Correlation evaluation between clinical characteristics and survival model
We also grouped and tested the clinical features, the survival analysis after grouping still showed the same results as previously (Figure 6A). We can also see from the clinical correlation box graph that the risk scores of cluster1 and cluster2 and patients with different tumor stages also have significant differences (Figure 6B). In addition, according to the correlation heatmap, the expression level of apoptosis-related genes was significantly correlated with the risk score and two clusters, but not with the clinical characteristics (Figure 6C). Then, we studied the correlation between risk score and immunity, as shown in Figure 6D.
Figure 6: Correlation verification between risk model and clinical characteristics.
We can see from the figure, consistent with the foregoing, the infiltration of Dendritic cells and Mast cells decreased with the increase of risk score. In addition, Plasma cells, Monocytes and T cells CD4 memory showed the same trend. On the contrary, when the risk score increased, Macrophages M0, Macrophages M1, Neutrophils and NK cells showed an increasing trend. Thus, it can be seen that when the risk score increased, the body immunity showed a state of inhibition, indicating a poor survival prognosis. This result further proves the prediction ability of our model.
Lung cancer is a malignant tumor with highest incidence rate and mortality rate. However, the early diagnosis and treatment results are still not ideal, and the recurrence and metastasis rate after treatment are still not low. Thus, it is very important to study the pathogenesis of non-small cell lung cancer and find new method of diagnosis and treatment, especially LUAD, which accounts for a high proportion[12]. At present, the treatment of LUAD tends to be accurate and individualized[13, 14]. Nevertheless, in terms of the current clinical situation and treatment guidelines, the realization of accurate individualized treatment is very difficult. The surgical treatment of early LUAD patients did not achieve very ideal results. Lately, due to the widespread use of sequencing technology in cancer research, the diagnosis and treatment at the molecular level has gradually become a hot topic, and various prognostic predictors of LUAD have been proposed[15-18]. Using biomarkers to diagnose and predict survival prognosis has become a trend[13]. As a biological process, apoptosis is involved in the occurrence and development of tumors and plays an important role. As far as we know, there is still a lack of research on predicting the prognosis of LUAD patients with apoptosis-related genes. Therefore, it is of clinical significance to find apoptosis-related genes and establish prognosis prediction model.
In our study, we selected 10 apoptosis-related gene signatures based on enrichment analysis in MSigDB. Based on the expression level of these genes, we defined the apoptosis state of LUAD tissue and divided these tumor samples into two subgroups. Compared with cluster1, cluster2 showed apoptosis inhibition, immune cells infiltration also showed immune system inhibition, and the survival prognosis was significantly worse than cluster1. Then, based on TCGA database, a prognostic risk model of apoptosis-related genes in LUAD was established by using univariate and Lasso Cox regression analysis. Using this model, we can divide LUAD patients into high-risk and low-risk groups. Furthermore, by testing clinical data and risk model, we proved that risk score can be used as an independent predictor of LUAD. Univariate, multivariate Cox analysis and ROC curve results also proved this conclusion. We then demonstrated once again the predictive power of our prognostic model in the test set. Finally, we also analyzed the correlation between clinical characteristics and prognostic model. Our research may help clinicians make individualized and effective treatment decisions, and provide help for further research.
However, it should be acknowledged that there are still some deficiencies in our study. First, we established a prognostic model through traditional statistical methods and then evaluate it. Although these methods have been confirmed in some studies, there is still room for improvement in further research in the future. Second, in our study, further experiments are needed to clarify the biological function of apoptosis-related genes in LUAD, which may help us to deeply understand the specific mechanism.
In short, we established a new apoptosis-related survival model to stratify the risk of LUAD patients and evaluate their prognosis. The model is composed of 10 apoptosis-related genes (DNM1L, SOD1, TGFB2, BIRC3, KRT18, BIK, DNAJA1, TIMP1, BCL2L10, CYLD) in LUAD, and may help to realize the individualized treatment and management of LUAD patients.
We used R software (version 4.0.3) to perform all statistical analysis. And the statistical analysis in this study is mostly based on online database. The Kaplan-Meier survival analysis was used to evaluate the prognosis, Lasso-cox regression analysis to establish the model and Univariate and multivariate Cox regression analysis to verify whether it can be used as an independent factor. ROC curves were used to assess the predictive accuracy for survival. We considered P < 0>
Ethics approval and consent to participate
All the gene expression data used the data that had been normalized. For this study, only open-access data were used, which excluded the requirement of authorization from the Ethics Committee.
Release of consent
Not applicable.
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Competing interests
The authors report no conflicts of interest in this work.
Funding
This study was funded by Natural Science Foundation of Zhejiang Province（LY21H160059）
Authors' contributions
Wei Zhang and wrote the manuscript. Wentao Zhu and Suwei Xu collected and analyzed the raw data. Wei Zhang and Yu Liu designed the whole work.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.
Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.
Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.
We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.
The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.
Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.
Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.
Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.
Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.
Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.
This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.
Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.
As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.
Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.
International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.
Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.
Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.
I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
