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整合素 α 亚家族 mRNA 表达在结肠腺癌中的诊断和预后价值。

Diagnostic and prognostic values of integrin α subfamily mRNA expression in colon adenocarcinoma.

机构信息

Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China.

出版信息

Oncol Rep. 2019 Sep;42(3):923-936. doi: 10.3892/or.2019.7216. Epub 2019 Jun 28.

Abstract

The integrin α (ITGA) subfamily genes play a fundamental role in various cancers. However, the potential mechanism and application values of ITGA genes in colon adenocarcinoma (COAD) remain elusive. The present study investigated the significance of the expression of ITGA genes in COAD from the perspective of diagnosis and prognosis. A COAD RNA‑sequencing dataset was obtained from The Cancer Genome Atlas. The present study investigated the biological function of the ITGA subfamily genes through bioinformatics analysis. Reverse transcription‑quantitative polymerase chain reaction was applied to investigate the distribution of integrin α8 (ITGA8) expression in COAD tumors and adjacent normal tissues. Bioinformatics analysis indicated that ITGA genes were noticeably enriched in cell adhesion and the integrin‑mediated signaling pathway, and co‑expressed with each other. It was also revealed through observation that the majority of gene expression was significantly low in tumor tissues (P<0.05), and diagnostic receiver operating characteristic curves revealed that most of the genes could serve as significant diagnostic markers in COAD (P<0.05), especially ITGA8 which had a high diagnostic value with an area under curve (AUC) of 0.989 [95% confidence interval (CI) 0.980‑0.997] in COAD (P<0.0001). In addition, ITGA8 expression was verified in clinical samples and it was revealed that it was higher in adjacent normal tissues (P=0.041) compared to COAD tissues, and the AUC was 0.704 (95% CI, 0.577‑0.831; P<0.0085). Multivariate survival analysis indicated that integrin α (ITGA5) may be an independent prognostic indicator for COAD overall survival. Gene set enrichment analysis indicated that ITGA5 may participate in multiple biological processes and pathways. The present study revealed that ITGA genes were associated with the diagnosis and prognosis of COAD. The mRNA expression of ITGA8 may be a potential diagnosis biomarker and ITGA5 may serve as an independent prognosis indicator for COAD.

摘要

整合素 α(ITGA)亚家族基因在各种癌症中起着至关重要的作用。然而,ITGA 基因在结肠腺癌(COAD)中的潜在机制和应用价值仍不明确。本研究从诊断和预后的角度探讨了 ITGA 基因在 COAD 中的表达意义。从 The Cancer Genome Atlas 获得了 COAD 的 RNA 测序数据集。本研究通过生物信息学分析研究了 ITGA 亚家族基因的生物学功能。应用逆转录-定量聚合酶链反应(RT-qPCR)研究了整合素α8(ITGA8)在 COAD 肿瘤组织和相邻正常组织中的表达分布。生物信息学分析表明,ITGA 基因在细胞黏附和整合素介导的信号通路中明显富集,并且相互共表达。通过观察还发现,大多数基因在肿瘤组织中的表达明显较低(P<0.05),诊断受试者工作特征曲线(ROC)显示,大多数基因可作为 COAD 的显著诊断标志物(P<0.05),尤其是 ITGA8,其在 COAD 中的曲线下面积(AUC)为 0.989[95%置信区间(CI)0.980-0.997],具有较高的诊断价值(P<0.0001)。此外,在临床样本中验证了 ITGA8 的表达,结果显示其在相邻正常组织中的表达高于 COAD 组织(P=0.041),AUC 为 0.704(95%CI,0.577-0.831;P<0.0085)。多变量生存分析表明,整合素α(ITGA5)可能是 COAD 总生存期的独立预后指标。基因集富集分析表明,ITGA5 可能参与多种生物学过程和途径。本研究揭示了 ITGA 基因与 COAD 的诊断和预后相关。ITGA8 的 mRNA 表达可能是潜在的诊断生物标志物,而 ITGA5 可能是 COAD 的独立预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1b5/6667841/b953fb809054/or-42-03-0923-g00.jpg

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