Revising the Role of Integrin Subunit β4 Expression in Colon Cancer Progression and Survival: A Retrospective Study

Abstract

Background: Integrin subunit β4 (β4) has been proposed to play an important role in colon cancer progression through its involvement in hemidesmosome disassembly processes and tumor cell migration. However, no consensus has yet been achieved regarding its association with clinical outcomes, particularly in colon cancer. The aim of this study was to reveal the relation between β4 expression and clinicopathological features and colon cancer outcomes.Methods: Expression of β4 was assessed by immunohistochemistry in a large cohort of 651 colon cancer patients, the largest colon cancer cohort so far. Chi-square tests were used to study the association between β4 expression and clinicopathological features while its relation with disease-free survival was assessed by Cox proportional hazard models. Furthermore, a potential relation between levels of ITGB4 expression and patient outcomes was also investigated with the TCGA dataset.Results: No association between β4 expression and disease-free survival was encountered (P = 0.767), which disputes the role of β4 as a biomarker of malignant behavior in colon cancer. Strikingly, loss of β4 expression was instead associated with advanced pathological tumor (pT) stage of the primary tumor. Only 17.9% of the pT1 tumors displayed weak β4 expression level versus 28.1% of pT4 tumors, and 25.0% of the pT1 tumors had a high expression level versus 8.6% of the pT4 tumors (P = 0.012). Additionally, no relation was observed between β4 expression and colon cancer stage (P = 0.138), tumor differentiation grade (P = 0.097) or mismatch repair (MMR) status (P = 0.878).Conclusions: Contradictory reports have suggested opposite roles for β4 expression in (colon) cancer progression. In the present large cohort of colon cancer patients we found that β4 expression was not associated with worse clinical prognosis and tumor differentiation grade, but decreased with advanced pathological tumor stage. Future studies should establish whether loss of β4 expression promotes invasive characteristics of colon cancer cells.