Wei Luwei, Yin Fuqiang, Zhang Wei, Li Li
Department of Gynecologic Oncology, Affiliated Tumor Hospital of Guangxi Medical University Life Sciences Institute, Guangxi Medical University Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, PR China.
Medicine (Baltimore). 2017 Mar;96(12):e6345. doi: 10.1097/MD.0000000000006345.
Cancer stem cells (CSCs) are considered to be the root of carcinoma relapse and drug resistance in ovarian cancer. Hunting for the potential CSC genes and explain their functions would be a feasible strategy to meet the challenge of the drug resistance in ovarian cancer. In this study, we performed bioinformatic approaches such as biochip data extraction and pathway enrichment analyses to elucidate the mechanism of the CSC genes in regulation of drug resistance. Potential key genes, integrins, were identified to be related to CSC in addition to their associations with drug resistance and prognosis in ovarian cancer. A total of 36 ovarian CSC genes involved in regulation of drug resistance were summarized, and potential drug resistance-related CSC genes were identified based on 3 independent microarrays retrieved from the Gene Expression Omnibus (GEO) Profiles. Pathway enrichment of CSC genes associated with drug resistance in ovarian cancer indicated that focal adhesion signaling might play important roles in CSC genes-mediated drug resistance. Integrins are members of the adhesion molecules family, and integrin subunit alpha 1, integrin subunit alpha 5, and integrin subunit alpha 6 (ITGA6) were identified as central CSC genes and their expression in side population cells, cisplatin-resistant SKOV3 (SKOV3/DDP2) cells, and cisplatin-resistant A2780 (A2780/DDP) cells were dysregulated as measured by real-time quantitative polymerase chain reaction. The high expression of ITGA6 in 287 ovarian cancer patients of TCGA cohort was significantly associated with poorer progression-free survival. This study provide the basis for further understanding of CSC genes in regulation of drug resistance in ovarian cancer, and integrins could be a potential biomarker for prognosis of ovarian cancer.
癌症干细胞（CSCs）被认为是卵巢癌复发和耐药的根源。寻找潜在的CSC基因并解释其功能将是应对卵巢癌耐药挑战的可行策略。在本研究中，我们进行了生物信息学方法，如生物芯片数据提取和通路富集分析，以阐明CSC基因在耐药调控中的机制。除了与卵巢癌的耐药性和预后相关外，还鉴定出潜在的关键基因整合素与CSC相关。总共总结了36个参与耐药调控的卵巢CSC基因，并基于从基因表达综合数据库（GEO）检索到的3个独立微阵列鉴定出潜在的耐药相关CSC基因。卵巢癌中与耐药相关的CSC基因的通路富集表明，粘着斑信号可能在CSC基因介导的耐药中起重要作用。整合素是粘附分子家族的成员，整合素亚基α1、整合素亚基α5和整合素亚基α6（ITGA6）被鉴定为核心CSC基因，通过实时定量聚合酶链反应测量，它们在侧群细胞、顺铂耐药的SKOV3（SKOV3/DDP2）细胞和顺铂耐药的A2780（A2780/DDP）细胞中的表达失调。TCGA队列中287例卵巢癌患者中ITGA6的高表达与较差的无进展生存期显著相关。本研究为进一步了解CSC基因在卵巢癌耐药调控中的作用提供了依据，整合素可能是卵巢癌预后的潜在生物标志物。
