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Research Article | DOI: https://doi.org/10.31579/2690-1919/220
1 IInd Surgery Clinic, Timisoara Emergency County Hospital, Romania.
2 “Victor Babes” University of Medicine and Pharmacy Timisoara Romania.
3 IInd Obstetric and Gynecology Clinic “Dominic Stanca” Cluj-Napoca, Romania.
4 “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Romania.
*Corresponding Author: Adelina Clim and Ionel Nati, IInd Obstetric and Gynecology Clinic “Dominic Stanca” Cluj-Napoca, Romania.
Citation: Flaviu I. Faur, Adelina Clim, Ionel Nati and Amadeus Dobrescu. (2022). Lipid Profile an Important Risk Factor in Patients with Ovarian Tumors: A Meta-Analysis. J Clinical Research and Reports, 10(1); DOI:10.31579/2690-1919/220
Copyright: © 2022, Adelina Clim and Ionel Nati. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 02 December 2021 | Accepted: 21 December 2021 | Published: 06 January 2022
Keywords: ovarian tumor; lipid profile; total cholesterol; triglycerides; low-density lipoprotein
Introduction
In the literature ovarian tumors are know to be one of the deadliest gynecological malignancies [1-4]. In US this type of malignancy represents 2.3 % of all cancer-related death and about 4 % of all new cancer cases among women. There are several studies that have reported the role of lipid profiles and it’s role in ovarian tumorigenesis. Fatty acids are essential for cancer cells progression[4-8]. In our study we investigated the true differance in circulating lipid profiles (total cholesterol TC, triglyceride TG, high-density lipoprotein cholesterol HDL, low density lipoprotein cholesterol LDL) among patients with and without ovarian tumors (OT) using a meta-analytical approach.
Methods
The meta-analysis was conducted using the MOOSE guidelines. PubMed, EMBASE and Cochrane Library were extensively searched (with a period of publication restriction between 2007 and 2019) to indentify published studies using the following keywords: “ total cholesterol ”, “high-density lipoprotein”, “ triglycerides ”, “ low-density lipoprotein ”, “ ovarian cancer”, “ ovarian tumor ”, “ lipid profile ”. The search methodology is shown in Fig. 1 and all references of retrieved articles were searched manually.
Results
Seven studies, involving 1542 OT cases and 2195 non-cases of OT were included in this meta-analysis and I² statistics ranged between 97 and 99%. Mean circulating TC and HDL were significantly lower among OT cases compared to non-OT cases (P<0.04 and P<0.005).
Conclusion
There is a modest significant association between circulating HDL and risk of ovarian tumor but it is crucial to elucidate the implications of HDL in tumor manifestations and growth.
In the literature ovarian tumors are know to be one of the deadliest gynecological malignancies. In US this type of malignancy represents 2.3 % of all cancer-related death and about 4 % of all new cancer cases among women. In the latest statistical cohort, there was an incidence of 11.6 cases/100.000 women per year, with an estimated 224.940 women living with this disease in the world. The simptomatology in ovarian tumors is hidden and about 70 % of patients are diagnosed in advanced stage, wich underlines that ovarian tumors are a serious public health concern. As we all know lipids are biologically important hydrophobic moleculs vital for energy storage, cell signalling and maintenance of cell membrane integrity. Lipids are transported in the bloodstream with the aid of lipoprotein. Lipids are widely distributed in cellular organells and used as biologically vital active molecules. There are several studies that have reported the role of lipid profiles and it’s role in ovarian tumorigenesis. Fatty acids are essential for cancer cells progression. In our study we investigated the true differance in circulating lipid profiles (total cholesterol TC, triglyceride TG, high-density lipoprotein cholesterol HDL, low density lipoprotein cholesterol LDL) among patients with and without ovarian tumors (OT) using a meta-analytical approach.
The meta-analysis was conducted using the MOOSE guidelines. PubMed, EMBASE and Cochrane Library were extensively searched ( with a period of publication restriction between 2007 and 2019) to indetify published studies using the following keywords: “ total cholesterol ”, “high-density lipoprotein”, “ triglycerides ”, “ low-density lipoprotein ”, “ ovarian cancer”, “ ovarian tumor ”, “ lipid profile ”. The search methodology is shown in Fig. 1 and all references of retrieved articles were searched manually.
Criteria of inclusion in the meta-analysis:
The magnitude of variation across studies was assessed ussing I² test statistics and a random-effects model was used to obtain mean estimates under considerable heterogeneity (I²-test >50% or P<0>
Name of authors, year of publication (after 2007), country, study population, sample size, lipid profile, criteria for case definition, mean values ( with standard deviation SD, standard error of mean SEM, confidence interval CI) of serum lipid profile (TC, LDL, HDL, TG) were extracted independently by two reviewers and differences in data extractions were resolved in recourse to a third reviewer. We establish that mean values of TC were transformed to mg/dl, but TG, HDL and LDL were transformed to mmol/L. Also, all values reported as SEM and CI were transformed into SD.
We have done a literature research and identified through electronic catalogue searching on PUBMED, EMBASE, COCHRANE library a number of 1704 studies from the primary ture search. About 384 were duplicates and we have excluded 1201 after examining titles and abstracts. After full-text evaluation were excluded 112 studies and in this meta-analysis we included 7 studies (Table 1) that matched the inclusion criteria comprising 1542 ovarian tumor cases and 2195 non-ovarian tumor cases.
| Authors | Year | Country | Cases | Control | Lipid profile | Ascertainment of ovarian tumor cases | Classification |
| Bukhari et al. | 2016 | Pakistan | 30 | 30 | TC, TG, HDL, LDL | Hospital/Medical record | NR |
| Camuzcuoglu et al. | 2009 | Turkey | 24 | 29 | TC, TG, HDL, LDL | Hospital/Medical record | FIGO |
| Delimaris et al. | 2007 | Greece | 15 | 30 | TC, HDL, LDL | Hospital confirmed | FIGO |
| Chen et al. | 2017 | China | 573 | 1146 | TG, HDL | Histopathological examinations | FIGO |
| Knapp et al. | 2017 | Poland | 74 | 81 | TC, TG | Hospital/Medical record | NR |
| Melvin et al. | 2012 | Sweden | 786 | 829 | TC, TG, HDL, LDL | Histopathological examinations | FIGO |
| Qadir et al. | 2008 | Pakistan | 40 | 50 | TC, TG, HDL, LDL | Hospital confirmed | FIGO |
1542 | 2195 |
(Table 1)
In our meta-analysis mean total cholesterol was significantly lower among ovarian tumors cases compare to non-ovarian tumors cases (P= 0.04) also mean HDl=L was significantly lower among OT cases compared to non-OT cases. All cases we stratified by age and this differences were insignificant. If we talk about mean TG and LDL the differences were insignificantly between OT and non-OT cases. As we mentioned we stratified our meta-analysis by age (Table 2). In table 2 we could observed that TG profile was significantly elevated among OT cases under 49 years old 0.059 [0.54, 0.63] mmol/L P<0>P<0>
In a subgroup of cases with malignant OT and/or advanced tumors TC was significantly lower (P<0>
| TC (mg/dL) | D | TG (mmol/L) | D2 | HDL (mmol/L) | D3 | LDL (mmol/L) | D4 | |
| All studies | -16,52 [-32,43 ; -0,72] | ↓ | 0.063 [-0.19, 0.28] | ↔ | -0.24 | ↓ | 0.12 [-0.23, -0.09]* | ↔ |
| Age groups | ||||||||
| Young adults ( under 49 years) | -23,34 [-57,86; 12,12] | ↔ | 0.059 [0.54, 0.63]^ | ↑ | ≠ | ≠ | ||
| Old adults (over 49 years) | -19,63 [-47,12; 8,32] | ↔ | -0.04 [-0.3, 0.32] | ↔ | -.039 [-1.23, 0.38] | ↔ | 0.38 [0.23, 0.06]^ | ↑ |
| Type of tumor | ||||||||
| Benign | -13,21 [-39,32; 13,02] | ↔ | 0.02 [-0.20, 0.22] | ↔ | ≠ | |||
| Malignant | -36,98 [-69,87; -4,21]* | ↓ | 0.14[-0.02, 0.31] | ↔ | -0.59 [-0.68, -0.43] | ↓ | ≠ | |
| Stage of cancer | ||||||||
| Early (under II) | ≠ | ≠ | ≠ | ≠ | ||||
| Advanced (over III) | -27.12 [-81,34; 32,1] | ↔ | -0.23 [-0.64, 0.24] | ↔ | ≠ | ≠ | ||
| Type and/or Stage | ||||||||
| Benign and Early | 8,23 [-32,18; 50,12] | ↔ | 0.01 [-0.16, 0.22] | ↔ | -0.28 [-0.36, -0.18] | ↓ | ≠ | |
| Malignant and Advanced | -30,23[-60,56; | ↓ | -0.00 [-0.15, 0.18] | ↔ | -0.28 [-0.92, 0.28] | ↔ | ≠ | |
| Risk of Bias of included studies | -0,32]* | |||||||
| Low | -15,98 [-51,1; 19,2] | ↔ | 0.15 [-0.10, 0.39] | ↔ | -0.25 [-0.46, -0.03]* | ↓ | 0.23 [-0.16, 0.69] | ↔ |
| High | -16,2 [-31,2; -0,56]* | ↓ | -0.00 [-0.23. 0.25] | ↔ | -0.25 [-0.51, -0.04]* | ↓ | -0.23 [-0.29, 0.15]^ | ↓ |
(Table 2)
Mean difference and 95% CI of Lipid Profile between cases and non-cases of ovarian tumors
D-direction of mean difference relative to non-ovarian tumour cases; TC-Total cholesterol; TG-Triglycerides; HDL-High density lipoprotein; LDL-Low
density lipoprotein
*p < 0>
^p < 0>
≠studies were insufficient to carry out the meta-analysis
↑mean difference significantly higher among cases than non-cases of ovarian tumour
↓mean difference significantly lower among cases than non-cases of ovarian tumour
↔mean difference insignificantly different between cases than non-cases of ovarian tumour
There are few metaanalytical studies in the literature about this topic. Lipid profile it is an important risk factor in ovarian tumorigenessis [9-14]. Total cholesterol and HDL profiles were significantly lower among patients with ovarian tumors but the profile level of TG and LDL were insignificant. Circulating lipid profiles are largely subject to alterations in occurrence of tumor events. In our meta-analysis we highlight the significance of lipids in OT outcomes. The strong affinity of cancer cells for sterols and lipids makes lipid metabolism a critical factor in cancer signaling and excessive production of lipogenic enzymes has been observed in several cancers and is linked with cancer severity and recurrance. In our meta-analysis we observed that HDL was inversely related to OT risk. This kind of observation was related by Gadomska et al. In a multidimensional analysis. As we all know the anti-inflammatory properties of HDL in inhibiting cell proliferatrion and apoptosis are crucial in preventing the increased intracellular oxidative stress that is a critical step in cancer pathogenesis [15,16]. Decreased HDL levels are associated with increased levels of proinflammatory cytokines including tumor necrosis factor-alpha and interleukin-6. Tumor cells express increased LDL receptor levels which lead to low LDL levels. Most studies included in our meta-analysis were cross-sectional and limited studies age-matched cases with controls in the eligible studies [17,18].
There is a modest significant association between circulating HDL and risk of ovarian tumor but it is crucial to elucidate the implications of HDL in tumor manifestations and growth and it’s important to highlights the role of serum lipid profile in diagnosis, prognosis and recurrence of the disease in future studies.
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