Cancer Management and Research (Dec 2021)
Low Density Lipoprotein Receptor (LDLR) and 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase (HMGCR) Expression are Associated with Platinum-Resistance and Prognosis in Ovarian Carcinoma Patients
Abstract
Xueyao Huang,1,2 Xuan Wei,1 Sijing Qiao,1,2 Xue Zhang,1,2 Rui Li,1 Shunxue Hu,3 Hongluan Mao,1,2 Peishu Liu1,2 1Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Peishu Liu; Hongluan MaoDepartment of Obstetrics and Gynecology, Qilu Hospital of Shandong University, No. 107 Wen Hua Xi Road, Jinan, Shandong, 250012, People’s Republic of ChinaTel +8618560081988; Tel +8618560082027Email [email protected]; [email protected]: 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
