Elevated integrin α6 expression is involved in the occurrence and development of lung adenocarcinoma, and predicts a poor prognosis: a study based on immunohistochemical analysis and bioinformatics

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.