Purpose: The efficacy of post-surgery platinum-based chemotherapy, the primary choice for the treatment of ovarian cancer (OC), is greatly reduced by the development of drug-resistance. In this study, we investigated the association of expression low-density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), two cholesterol metabolism-related proteins, in OC tissues and chemoresistance and patient prognosis.
Methods: Survival analysis using LDLR and HMGCR expression in the ovarian cancer patients using the dataset of Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was carried out online. A retrospective study was performed on 65 patients who had undergone surgery for ovarian cancer. In addition, patients were divided into 2 groups: platinum resistance group and platinum sensitivity group. Serum lipid metabolism data were collected and analyzed. Protein expressions of LDLR and HMGCR in ovarian cancer tissue were detected by immunohistochemistry.
Results: Online survival analysis showed that patients with higher LDLR expression had poorer prognosis than those with lower LDLR expression in ovarian cancer cells, while a higher HMGCR expression was associated with better OC prognosis. Overall survival (OS) and disease-free survival (DFS) were lower in patients with higher LDLR levels (OS: P =0.046, DFS: P =0.009). Platinum-resistant patients had higher levels of low-density lipoprotein (LDL) and cholesterol in serum as compared with platinum-sensitive patients (P < 0.001). Immunohistochemistry showed that LDLR expression was high and HMGCR was low in platinum-resistant patients.
Conclusion: The expression of LDLR and HMGCR proteins, involved in the regulation of cholesterol metabolism and the plasma LDL and cholesterol levels were significantly different in platinum-resistant and platinum-sensitive ovarian cancer patients. We postulate that cholesterol metabolic reprogramming might play a role in platinum resistance in ovarian cancer.
Keywords: LDLR, HMGCR, ovarian cancer, platinum resistance, cholesterol metabolism