Liu Longyang, Lv Jin, Lin Zhongqiu, Ning Yingxia, Li Jing, Liu Ping, Chen Chunlin
Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
Front Mol Biosci. 2022 Feb 9;8:785922. doi: 10.3389/fmolb.2021.785922. eCollection 2021.
The prognosis of epithelial ovarian cancer (EOC) is poor, and the present prognostic predictors of EOC are neither sensitive nor specific. The aim of this study was to search the prognostic biomarkers of EOC and to investigate the expression of G protein-coupled receptor kinase 5 (GRK5) and actin alpha cardiac muscle 1 (ACTC1) in EOC tissues (both paraffin-embedded and fresh-frozen tissues) and to explore their association with clinicopathological parameters and prognostic value in patients with EOC. A total of 172 paraffin-embedded cancer tissues of EOC patients diagnosed and operated at the memorial hospital of Sun Yat-sen University between December 2009 and March 2017 and 41 paratumor tissues were collected and the expression of GRK5 and ACTC1 was examined using immunohistochemistry. Furthermore, 16 fresh-frozen EOC tissues and their matched paratumor tissues were collected from the Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, between August 2013 and November 2019 and subjected to reverse-transcription quantitative PCR analysis to detect the mRNA expression of GRK5 and ACTC1. The expression of GRK5 and ACTC1 was both higher in cancer tissues than in paratumor tissues. GRK5 expression was positively correlated with ACTC1 expression. In addition, GRK5, ACTC1, and GRK5/ACTC1 expression was associated with the recurrence-free survival and overall survival of EOC patients. Furthermore, multivariate logistic regression analysis indicated that GRK5+/ACTC1+ co-expression, intestinal metastasis, postoperative chemotherapy, platinum resistance, and hyperthermic intraperitoneal chemotherapy were independent prognostic factors of EOC. GRK5 and ACTC1 are both upregulated in EOC compared with those in paratumor tissues. The co-expression of GRK5+/ACTC1+ rather than GRK5 or ACTC1 is an independent prognostic biomarker of EOC.
上皮性卵巢癌(EOC)的预后较差,目前EOC的预后预测指标既不敏感也不特异。本研究的目的是寻找EOC的预后生物标志物,研究G蛋白偶联受体激酶5(GRK5)和心肌肌动蛋白α1(ACTC1)在EOC组织(石蜡包埋组织和新鲜冰冻组织)中的表达,并探讨它们与EOC患者临床病理参数的相关性及预后价值。收集了2009年12月至2017年3月在中山大学附属肿瘤医院诊断并接受手术的172例EOC患者的石蜡包埋癌组织和41例癌旁组织,采用免疫组织化学法检测GRK5和ACTC1的表达。此外,收集了2013年8月至2019年11月在南方医科大学附属中医医院的16例新鲜冰冻EOC组织及其配对的癌旁组织,进行逆转录定量PCR分析以检测GRK5和ACTC1的mRNA表达。GRK5和ACTC1在癌组织中的表达均高于癌旁组织。GRK5表达与ACTC1表达呈正相关。此外,GRK5、ACTC1及GRK5/ACTC1表达与EOC患者的无复发生存率和总生存率相关。进一步的多因素逻辑回归分析表明,GRK5+/ACTC1+共表达、肠转移、术后化疗、铂耐药及热灌注化疗是EOC的独立预后因素。与癌旁组织相比,GRK5和ACTC1在EOC中均上调。GRK5+/ACTC1+共表达而非GRK5或ACTC1是EOC的独立预后生物标志物。