Huang Xueyao, Wei Xuan, Qiao Sijing, Zhang Xue, Li Rui, Hu Shunxue, Mao Hongluan, Liu Peishu
Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China.
Shandong University, Jinan, Shandong, 250012, People's Republic of China.
Cancer Manag Res. 2021 Dec 6;13:9015-9024. doi: 10.2147/CMAR.S337873. eCollection 2021.
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.
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.
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: =0.046, DFS: =0.009). Platinum-resistant patients had higher levels of low-density lipoprotein (LDL) and cholesterol in serum as compared with platinum-sensitive patients (<0.001). Immunohistochemistry showed that LDLR expression was high and HMGCR was low in platinum-resistant patients.
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.
手术后铂类化疗是卵巢癌（OC）治疗的主要选择，但耐药性的出现使其疗效大大降低。在本研究中，我们调查了两种胆固醇代谢相关蛋白——低密度脂蛋白受体（LDLR）和3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）在OC组织中的表达、与化疗耐药性及患者预后的关系。
利用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）的数据在线分析LDLR和HMGCR表达与卵巢癌患者生存情况的关系。对65例行卵巢癌手术的患者进行回顾性研究。此外，将患者分为两组：铂耐药组和铂敏感组。收集并分析血清脂质代谢数据。通过免疫组织化学检测卵巢癌组织中LDLR和HMGCR的蛋白表达。
在线生存分析显示，在卵巢癌细胞中，LDLR表达较高的患者预后比LDLR表达较低的患者差，而HMGCR表达较高与OC患者较好的预后相关。LDLR水平较高的患者总生存期（OS）和无病生存期（DFS）较低（OS：=0.046，DFS：=0.009）。与铂敏感患者相比，铂耐药患者血清中的低密度脂蛋白（LDL）和胆固醇水平更高（<0.001）。免疫组织化学显示，铂耐药患者中LDLR表达高而HMGCR表达低。
参与胆固醇代谢调节的LDLR和HMGCR蛋白表达以及血浆LDL和胆固醇水平在铂耐药和铂敏感的卵巢癌患者中存在显著差异。我们推测胆固醇代谢重编程可能在卵巢癌铂耐药中起作用。
