Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Zhejiang University, Taizhou, 317000, China.
Department of Cardiothoracic Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Taizhou, 317000, China.
J Cancer Res Clin Oncol. 2019 Jul;145(7):1681-1693. doi: 10.1007/s00432-019-02907-1. Epub 2019 Jun 7.
To study integrin α6 expression in lung adenocarcinoma tissue through comparison with matching adjacent non-cancerous tissues as well as elucidating the correlation between integrin α6 expression with the clinical parameters of lung adenocarcinoma. We also explore the signal pathways associated with integrin α6 up-regulation.
The clinical data, cancer tissues, and adjacent non-cancerous tissues of 30 patients diagnosed with lung adenocarcinoma were collected from Taizhou Hospital in Zhejiang Province, China, in 2010. The protein levels of integrin α6 were determined by immunohistochemistry methods. mRNA data of 85 lung adenocarcinoma tissues and 14 normal tissues as well as clinical results were collected from GEO30219. We also collected mRNA data of 533 lung adenocarcinoma tissues and 59 normal tissues as well as the clinical results of 522 patients with lung adenocarcinoma from the Cancer Genome Atlas (TCGA) database. The differences in protein and mRNA levels in cancer tissues and non-cancerous tissues were analyzed, and we subsequently investigated the association between integrin α6 expression and key parameters indicating lung adenocarcinoma progression and overall survival rate. Additionally, the possible pathways involved in the up-regulation of integrin α6 were analyzed by GSEA.
The protein levels of integrin α6 in lung adenocarcinoma tissues were significantly higher than those in adjacent tissues (p < 0.01), and were positively correlated with the grade and T stage of lung adenocarcinoma (p < 0.05). Patients with low integrin α6 protein levels had higher survival rates (p < 0.05). The analysis of gene chip data from the TCGA database also showed that the integrin α6 mRNA level was significantly correlated with T stage (p < 0.05), overall survival (OS) rate (p < 0.01), and disease-free survival (DFS) rate (p = 0.005). GSEA gene enrichment analysis identified a series of pathways that may be associated with integrin α6 up-regulation, including the AGR, PYK2, ECM, and PTEN pathways.
Integrin α6 plays an important role in the occurrence and progression of lung adenocarcinoma and may act as a prognostic predictor of lung adenocarcinoma in patients. Based on the results of the present study, integrin α6 may be a potential target gene for the treatment of lung adenocarcinoma.
通过与匹配的相邻非癌组织进行比较，研究整合素 α6 在肺腺癌组织中的表达，并阐明整合素 α6 表达与肺腺癌临床参数之间的相关性。我们还探讨了与整合素 α6 上调相关的信号通路。
收集 2010 年中国浙江省台州医院 30 例肺腺癌患者的临床资料、癌组织和相邻非癌组织。采用免疫组织化学方法检测整合素 α6 的蛋白水平。从 GEO30219 数据库中收集了 85 例肺腺癌组织和 14 例正常组织的 mRNA 数据以及临床结果，还从癌症基因组图谱（TCGA）数据库中收集了 533 例肺腺癌组织和 59 例正常组织的 mRNA 数据以及 522 例肺腺癌患者的临床结果。分析癌组织和非癌组织中蛋白和 mRNA 水平的差异，随后研究整合素 α6 表达与肺腺癌进展和总生存率的关键参数之间的关系。此外，通过 GSEA 分析了可能参与整合素 α6 上调的途径。
肺腺癌组织中整合素 α6 的蛋白水平明显高于相邻组织（p<0.01），且与肺腺癌的分级和 T 分期呈正相关（p<0.05）。整合素 α6 蛋白水平低的患者生存率更高（p<0.05）。TCGA 数据库的基因芯片数据分析也表明，整合素 α6 mRNA 水平与 T 分期显著相关（p<0.05）、总生存率（OS）率（p<0.01）和无病生存率（DFS）率（p=0.005）。GSEA 基因富集分析鉴定了一系列可能与整合素 α6 上调相关的途径，包括 AGR、PYK2、ECM 和 PTEN 途径。
整合素 α6 在肺腺癌的发生和发展中起重要作用，可能是肺腺癌患者的预后预测因子。基于本研究结果，整合素 α6 可能是肺腺癌治疗的潜在靶基因。
