CD5 and CD6 as immunoregulatory biomarkers in non-small cell lung cancer

Background: The study of immune surveillance in the tumour microenvironment is leading to the development of new biomarkers and therapies. The present research focuses on the expression of CD5 and CD6 - two lymphocyte surface markers involved in the fine tuning of TCR signaling - as potential prognostic biomarkers in resectable stages of non-small cell lung cancer (NSCLC). Methods: CD5 and CD6 gene expression was analysed by reverse transcription quantitative polymerase chain reaction (RTqPCR) in 186 paired fresh frozen tumour and normal tissue samples of resected NSCLC. Results: Patients with higher CD5 expression had significantly increased overall survival (OS, 49.63 vs. 99.90 months, P=0.013). CD5 expression levels were correlated to CD4 infiltration and expression levels, and survival analysis showed that patients with a higher CD5/CD4+ ratio had significantly improved prognosis. Multivariate analysis established CD5 expression as an independent prognostic biomarker for OS in early stages of NSCLC (HR=0.554; 95% CI, 0.360-0.853; P=0.007). Further survival analysis of NSCLC cases (n=97) from The Cancer Genome Atlas (TCGA) database, confirmed the prognostic value of both CD5 and CD6 expression although CD6 expression alone did not reach significant prognostic value in our NSCLC training cohort. Conclusions: Our data support further studies on CD5 and CD6 as novel prognostic markers in resectable NSCLC and other cancer types (i.e., melanoma), as well as a role for these receptors in immune surveillance.