Non-Small Cell Lung Cancer (NSCLC) represents almost 80% of lung cancer cases. Despite the advances achieved in the last years, there is still a lack of knowledge concerning tumour microenvironment. This research is focused on two immunoregulatory genes, CD5 and CD6 as potential prognostic biomarkers in resectable NSCLC.
CD5 and CD6 gene expression was analysed by RTqPCR in 201 paired fresh-frozen tumour and normal tissue samples of resected NSCLC (training cohort). The Cancer Genome Atlas (TCGA) database was used to obtain an independent validation cohort with available gene expression data for normal and tumour tissue. Relative gene expression was calculated by Pfaffl formula. Prognostic value was assessed by Cox regression and Kaplan-Meier curves (log rank-test), considering significant p < 0.05.
Training cohort consisted mainly of men, current or former smokers, with good performance status (PS = 0). Survival analyses showed that patients with higher CD5 expression had significantly increased overall survival (OS, 53.3 vs. NR months, p = 0.011). A multivariate analysis reported that CD5 expression could be established as an independent prognostic biomarker for OS in early-stage NSCLC [HR = 0.539; 95% CI, 0.329-0.883; p = 0.014]. Survival analyses performed on 97 patients from TCGA database confirmed that higher expression levels of both CD5 and CD6 had a significant prognostic value for relapse-free survival (34.98 vs. 75.57 months, p = 0.033; 25.31 vs. 75.57 months, p = 0.020, respectively) and OS (40.49 vs. 77.97 months, p = 0.038; 39.02 vs. 77.97 months, p = 0.034, respectively). Therefore, these analyses support that NSCLC patients with higher expression levels of CD5 are associated with better outcomes. Besides, CD6 could potentially be a prognostic biomarker.
Our results support a role of the inmmunodulatory receptor CD5 as an independent prognostic biomarker in resectable NSCLC. Supported from Fundació La Marató TV3 (201319-30), ISCIII (PI12-02838 and PI15-00753), and MECD (SAF2016-80535-R) -co-financed by European Development Regional Fund. FA and IS are recipients of fellowships from ISCIII (Sara Borrell Program; CD15/00016) and Portuguese FCT (SFRH/BD/75738/2011), respectively.
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Legal entity responsible for the study
Fundación para la Investigación del Hospital General Universitario de Valencia.
Supported from Fundació La Marató TV3 (201319-30), Instituto de Salud Carlos III (PI12-02838 and PI15-00753), and MECD (SAF2016-80535-R) -co-financed by European Development Regional Fund. FA and IS are recipients of fellowships from ISCIII (Sara Borrell Program; CD15/00016) and Portuguese Fundação para a Ciência e a Tecnologia (SFRH/BD/75738/2011), respectively.
All authors have declared no conflicts of interest.