ITGB4 is a novel prognostic factor in colon cancer
ITGB4 is a novel prognostic factor in colon cancer
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ITGB4是结肠癌的新预后因素
DOI：
10.7150/jca.29269
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Zhao, Zengren
中科院分区：
文献类型：
--
作者：
Li, Meng;Jiang, Xia;Zhao, Zengren
据报道，整合素β 4（ITGB 4）与癌有关。目前，ITGB 4在结肠癌中的特征已被确定，但其临床意义尚不十分清楚。在本研究中，我们利用NCBI Gene Expression Omnibus（GEO）和The Cancer Genome Atlas（TCGA）数据库中的大型公共数据集，并收集本中心的临床样本，研究ITGB 4在结肠癌中的转录表达，然后探讨ITGB 4与临床病理特征和总生存率的关系。统计学分析表明ITGB 4 mRNA在结肠癌中表达显著上调。ITGB 4高表达与发病年龄大、肿瘤近端位置和高微卫星不稳定性（MSH）状态相关。Kaplan-Meier曲线和单因素分析显示ITGB 4高表达与结肠癌不良的总生存率显著相关（HR=1.292，95%CI=1.084-1.540，P=0.004）。校正年龄、性别、分期等混杂因素后，两组间差异有统计学意义（校正HR=1.254，95%CI=1.050-1.497，P=0.012）。对ITGB 4共表达基因的注释表明，细胞生长、细胞迁移的正调控和凋亡信号通路可能参与了ITGB 4在结肠癌发生发展中的潜在机制。本研究还探讨了ITGB 4在结肠癌中异位表达的分子调控机制，结果表明ITGB 4可能通过转录因子FOSL 1（FOS like 1，AP-1 Transcription Factor Subunit）及其启动子低甲基化而上调。ITGB 4可能成为结肠癌个体化治疗的靶点和预后指标。
Integrin beta 4 (ITGB4) has been reported to be involved in carcinomas. Currently, ITGB4 has been characterized in colon cancer, however, its clinical significance is not very clear. In the present study, we utilized the large public datasets from NCBI Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and collected clinical samples in our center to investigate the transcriptional expressions of ITGB4 in colon cancer, and then explored the associations of ITGB4 with clinicopathological features and overall survival. The statistical analyses suggested that ITGB4 mRNA expressions were up-regulated significantly in colon cancer. High ITGB4 expression was observed to be associated with elder onset age, proximal tumor location, and high microsatellite instability (MSH) status. Further, Kaplan-Meier curves and univariate analysis demonstrated high ITGB4 expression was significantly associated with unfavorable overall survival in colon cancer (HR=1.292, 95%CI=1.084-1.540, P=0.004). And significant association was also found after adjusting the confounding factors including age, gender, and stage (adjusted HR=1.254, 95%CI=1.050-1.497, P=0.012). The annotation of ITGB4 co-expressed genes suggested the pathways including cell growth, positive regulation of cell migration, and apoptotic signaling might be involved in the potential mechanisms of ITGB4 in colon cancer development. The molecular regulation mechanism of ITGB4 ectopic expression in colon cancer was also explored and the results indicated that ITGB4 might be up-regulated by the transcription factor FOSL1 (FOS like 1, AP-1 Transcription Factor Subunit) and its promoter hypomethylation. Our results revealed that ITGB4 might be a therapeutic target and prognosis marker for individual therapy of colon cancer.