Study of the relationship between ovarian cancer and serum lipid levels, including TC, TG, HDL-C, LDL-C, and apolipoproteins, is of special interest and has sparked debate, and no consensus of their significance has been established. The aim of the present study was to evaluate the association between lipid profiles and ovarian cancer. We found that high level of preoperative HDL-C was a significant independent predictor of better PFS in ovarian cancer patients, whereas high level of LDL-C showed significant association with worse OS.
Cancer cells show specific alterations in different aspects of lipid metabolism, which are related to important cellular processes, including cell growth, proliferation, differentiation, and motility . As the primary mediators of cholesterol and lipid transport, lipoproteins are essential components of energy and lipid metabolism in the body, which may have direct effects on carcinogenesis. Some observational studies have indicated a relationship between HDL-C levels with some cancer types [19–23]. Epidemiological data have shown levels of HDL-C are significantly inversely associated with risk for multiple cancers [24–26]. The meta-analysis conducted by D. Zhang et al.  revealed an association between high HDL-C levels and lower ovarian cancer risk. Two retrospective studies also showed that low HDL-C levels were strongly correlated with severity of epithelial ovarian cancer [20, 28]. Although a meta-analysis including 25 studies with a total of 13,140 patients indicated that high serum HDL-C levels were associated with better OS and PFS in most of tumor types , the association between HDL-C and ovarian cancer still remains unclear. In our study, we have observed that patients with HDL-C level ≥ 1.19 mmol/L had a better PFS than patients with HDL-C level < 1.19 mmol/L (p = 0.001). HDLs play a key role in the reverse cholesterol transport (RCT), which can promote cholesterol removal from cancer cells, thus altering their homeostasis . In addition, HDLs are able to affect several other pathways, including oxidation, inflammation, apoptosis, angiogenesis and immunomodulatory activities which may be also relevant for cancer biology. The anti-oxidative properties of HDLs have been linked to their capacity to protect LDL from oxidative modification, which might be facilitated by HDL-associated apolipoproteins and enzymes, such as apoAⅠ, apoE2, apoAⅣ, apoJ, PON1 and LCAT [31–33]. Besides, HDLs are able to prevent the release of proinflammatory cytokines and to upregulate the expression of endothelial and leukocyte adhesion molecules, thus exerting anti- inflammatory effects. In addition, the anti-apoptotic effects of HDLs can be attributed to their ability to interact with caspase-3, a key factor of apoptotic pathway, or to induce upregulation of the anti-apoptotic Bcl-2 protein Bcl-xL [34, 35]. The pleiotropic activities of HDLs result into an overall anti-tumorigenesis effects.
Concerning LDL-C, discordant results were also found. One retrospective study from the United States showed that OS and PFS were longer for patients with normal LDL levels compared to those with elevated LDL, and LDL was suggested as a predictor of clinical outcome . In contrast, another retrospective study by Zhu et al  found that high levels of LDL was associated with a better recurrence-free survival in women with ovarian cancer. It should also be noted that a Mendelian randomization study of 22,406 women with ovarian cancer did not find any association between genetic variation in controlling LDL-C and risk of epithelial ovarian cancer . In this study, we found that patients with LDL-C level < 2.76 mmol/L had better OS than patients with LDL-C level ≥ 2.76 mmol/L (P = 0.028). As a main cholesterol transporter, LDL-C can provide cancer cells with lipids and cholesterol as a component for their proliferation. It was demonstrated that increased LDL receptor expressed in breast cancer tissue to increase the uptake of LDL-C from the bloodstream , and LDL promotes breast cancer progression by inducing cell proliferation, migration and loss of adhesion [40, 41]. However, the proliferation rates of ovarian carcinoma cell lines CAOV3 and SKOV3 remained unchanged when they were treated with LDL, which was stimulated by oxidized low-density lipoprotein (ox-LDL), accompanied by an induction of the expression of the antiapoptotic cytokine cardiotrophin 1 . Besides, it was found that ovarian cancer patients possessed high levels of ox-LDL compared with control subjects , which indicated that ox-LDL has an important role in ovarian cancer development. The oxidation of LDL results in the formation of peroxidation metabolites which cause structural alterations in DNA and decrease DNA repair capacity through their direct interaction with repair enzymes . Studies have showed a positive correlation between increased serum ox-LDL levels and an increased risk of colon, breast, and ovarian cancer [44–46]. Ox-LDL and its receptor LOX-1 activate the inflammatory pathway through nuclear factor-kappa B, leading to cell transformation. LOX-1 is important for maintaining the transformed state in developmentally diverse cancer cell lines and for tumor growth . However, the studies remained limited, detailed mechanisms of LDL need further investigation.
Several limitations of our study should be considered. Firstly, this was a retrospective study, and patients were excluded if data on serum lipid levels were not available. This may have caused selection bias. Secondly, serum lipid levels were measured only once before treatment, but they may change over time depending on the patient’s clinical course and disease status. Thirdly, the cohort of our study was relatively small and from a single center, further multi-center studies with more cases may be needed to minimize selection bias and potential confounding factors such as difference in geographic distribution. Despite these limitations, the use of Cox proportional hazards regression to perform a multivariate analysis is relative strengths of our study.