Lung cancer carries a poor prognosis and is the most common cause of
cancer-related death worldwide. The
integrin α6β4, a
laminin receptor, promotes
carcinoma progression in part by cooperating with various
growth factor receptors to facilitate invasion and
metastasis. In
carcinoma cells with mutant TP53, the
integrin α6β4 promotes cell survival. TP53 mutations and
integrin α6β4 overexpression co-occur in many aggressive
malignancies. Because of the high frequency of TP53 mutations in lung
squamous cell carcinoma (SCC), we sought to investigate the association of
integrin β4 expression with clinicopathologic features and survival in
non-small cell lung cancer (NSCLC). We constructed a
lung cancer tissue microarray and stained sections for
integrin β4 subunit expression using immunohistochemistry. We found that
integrin β4 expression is elevated in SCC compared with
adenocarcinoma (P<.0001), which was confirmed in external gene expression data sets (P<.0001). We also determined that
integrin β4 overexpression associates with the presence of venous invasion (P=.0048) and with reduced overall patient survival (hazard ratio, 1.46; 95% confidence interval, 1.01-2.09; P=.0422). Elevated
integrin β4 expression was also shown to associate with reduced overall survival in
lung cancer gene expression data sets (hazard ratio, 1.49; 95% confidence interval, 1.31-1.69; P<.0001). Using cBioPortal, we generated a network map demonstrating the 50 most highly altered genes neighboring ITGB4 in SCC, which included laminins,
collagens, CD151, genes in the EGFR and PI3K pathways, and other known signaling partners. In conclusion, we demonstrate that
integrin β4 is overexpressed in NSCLC where it is an adverse prognostic marker.