Yuan Jingsheng, Tan Lulu, Yin Zhijie, Tao Kaixiong, Wang Guobing, Shi Wenjia, Gao Jinbo
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Department of Pediatric Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.
Oncol Lett. 2019 Sep;18(3):2576-2583. doi: 10.3892/ol.2019.10533. Epub 2019 Jun 27.
Despite the fact that studies have revealed mechanisms underlying tumor chemoresistance, the functions of numerous potential chemoresistance-associated genes have yet to be elucidated. A bioinformatics analysis was conducted to screen differentially expressed genes (DEGs) across four types of chemoresistant tumors and functional enrichment analysis was used to examine the biological significance of these genes. Furthermore, a gene network was constructed using weighted gene co-expression network analysis to identify hub genes. A total of 6,015, 2,074, 2,141 and 954 differentially expressed genes were identified in estrogen receptor-negative breast cancer, ovarian cancer, rectal cancer and gastric cancer, respectively; however, only five of these DEGs were dysregulated in all four types of cancer. Functional enrichment analysis of the DEGs suggested that genomic stability and immune response are crucial determinants of tumor chemoresistance. In addition, 14, 8, 6 and 1 co-expressed gene modules were identified in estrogen receptor-negative breast cancer, ovarian cancer, rectal cancer and gastric cancer, respectively, and protein-protein interaction networks were created. The analysis identified only calcium-calmodulin-dependent protein kinase kinase 2, erythropoietin receptor, mitochondrial poly(A) RNA polymerase, α-parvin, and zinc finger and BTB domain-containing protein 44 to be dysregulated in all four cancer types, indicating varying mechanisms of chemoresistance in different tumor types. Furthermore, our analysis suggests that type I collagen α1, fibroblast growth factor 14 and major histocompatibility complex, class II, DR β1 potentially serve key roles in the development of chemoresistance. In conclusion, the present study proposes a simple and effective strategy for identifying genes involved in chemoresistance and predicting their potential functional roles, which may guide subsequent experimental studies.
尽管研究已经揭示了肿瘤化学抗性的潜在机制,但众多潜在的化学抗性相关基因的功能仍有待阐明。进行了一项生物信息学分析,以筛选四种类型的化学抗性肿瘤中的差异表达基因(DEG),并使用功能富集分析来检验这些基因的生物学意义。此外,利用加权基因共表达网络分析构建了一个基因网络,以识别枢纽基因。在雌激素受体阴性乳腺癌、卵巢癌、直肠癌和胃癌中分别鉴定出6015、2074、2141和954个差异表达基因;然而,这些DEG中只有5个在所有四种癌症类型中均失调。对DEG的功能富集分析表明,基因组稳定性和免疫反应是肿瘤化学抗性的关键决定因素。此外,在雌激素受体阴性乳腺癌、卵巢癌、直肠癌和胃癌中分别鉴定出14、8、6和1个共表达基因模块,并创建了蛋白质-蛋白质相互作用网络。分析仅确定钙调蛋白依赖性蛋白激酶激酶2、促红细胞生成素受体、线粒体聚腺苷酸RNA聚合酶、α-帕文以及含锌指和BTB结构域蛋白44在所有四种癌症类型中均失调,表明不同肿瘤类型中化学抗性的机制不同。此外,我们的分析表明,I型胶原α1、成纤维细胞生长因子14和主要组织相容性复合体II类DRβ1可能在化学抗性的发展中起关键作用。总之,本研究提出了一种简单有效的策略,用于识别参与化学抗性的基因并预测其潜在的功能作用,这可能指导后续的实验研究。