The study of the tumour microenvironment is leading to a better understanding of the evasion of immune surveillance and the development of new therapies. This research focuses on the analysis of immunoregulatory genes as potential prognostic biomarkers in resectable non-small cell lung cancer (NSCLC).
The expression of 8 genes involved in immune-regulation (PD-L1, PD-L2, IDO-1, IDO-2, ICOS-LG, CD5, CD6 and CD200) was analysed by RTqPCR in 257 paired fresh frozen tumour and normal tissue samples of resected NSCLC. Relative expression was calculated by Pfaffl formulae using ACTB, CDKN1B and GUSB as endogenous controls. Non-parametric tests were used for correlations between clinico-pathological and analytical variables and survival was assessed by Kaplan-Meier curves (long rank-test), considering significant p
Patient`s median age was 64 years, 82% were males, 88% were former or current smokers, 47% were adenocarcinomas (ADC). Patients with higher expression of CD5 and IDO2 had a significant increase in overall survival (OS, 53.3 vs NR months, p = 0.032; 51.9 vs NR months, p = 0.049, respectively). A signature combining the expression of CD5 and IDO2 was able to better prognosticate survival (40.4 vs NR months, p = 0.028). The multivariate analysis (including clinico-pathological and analytical variables) showed that this signature has independent prognostic information OS (HR = 0.553 [0.344-0.887], p = 0.016). Moreover, in the subgroup of ADC increased expression of CD5 and IDO2 was associated with longer OS as well as increased relapse-free survival (RFS, 19.1 vs NR months, p = 0.045; 18.8 and 67.0 months, p = 0.029, respectively). The multivariate analysis established this gene signature as an independent prognostic biomarker for OS (HR = 0.380 [0.166-0.872]; p = 0.026) and RFS (HR = 0.288 [0.139-0.597]; p = 0.002).
The analyses revealed the prognostic value of CD5 and IDO2, being their combination an independent prognostic marker in resectable NSCLC. Supported by grants from FEDER and PI12-02838 and PI15-00753 from ISCIII.
Clinical trial identification
Legal entity responsible for the study
Fundación para la Investigación del Hospital General Universitario de Valencia
Supported by grants from FEDER and PI12-02838 and PI15-00753 from ISCIII.
All authors have declared no conflicts of interest.