Prognostic impact of nectin-like molecule-5 (CD155) expression in Non-Small Cell Lung Cancer

Abstract Objective CD155, a transmembrane protein which inhibits antitumor immune responses, has been shown to be a predictor of worse clinical outcomes in non-small-cell lung cancer (NSCLC). However, its association with the prognosis, clinical and genomic characteristics of Latin American patients remains unexplored. Thus, this study characterizes CD155 expression in NSCLC. Materials and methods Tissue biopsies from 86 consecutive Latin American patients with locally advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Optimal cutoff values for CD155 expression were determined from receiver operating characteristic (ROC) curves according to the 2-year survival of patients with driver and non-driver mutations. Its association with clinicopathological features, median progression-free survival (mPFS), and median overall survival (mOS) was evaluated. Results The cutoff for high CD155 expression (CD155high) was 155 in the entire cohort and in patients without driver mutations, and 110 in patients with driver mutations. CD155 was detected in 84 patients (97.7%), more frequently (52.3%) and at higher levels (62.2%) in patients without driver mutations. EGFR L858R mutation was associated with lower CD155 expression than exon 19 deletion. CD155high patients had a significantly shorter mOS (13.0 vs 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Among patients without driver mutations, CD155high was related to significantly shorter mPFS (1.61 vs 6.40 months; HR: 2.04 [95% CI, 1.03–4.02]; p = 0.034) and mOS (2.92 vs 23.06 months; HR: 2.17 [95% CI, 1.07–4.42]; p = 0.032). In patients with driver mutations, CD155high was only borderline significant for shorter mOS (26.3 vs 52.0 months, HR: 2.39 [95% CI, 0.98–5.83]; p = 0.056). Conclusion CD155high is a predictor of worse survival outcomes in patients with advanced NSCLC, predominantly among those without onco-driver mutations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.