HIP1R Expression and Its Association with PD-1 Pathway Blockade Response in Refractory Advanced NonSmall Cell Lung Cancer: A Gene Set Enrichment Analysis

Huntingtin-interacting protein 1-related protein (HIP1R) plays an important role in the regulation of programmed death-ligand 1 (PD-L1). The aim of this study was to investigate the expression of HIP1R and confirm its predictive or prognostic roles in anti-PD-1 therapy in nonsmall cell lung cancer (NSCLC) patients. HIP1R and PD-L1 immunohistochemical expression was examined in 52 refractory advanced NSCLC patients treated with anti-PD-1 inhibitors. We performed gene set enrichment analysis (GSEA) to detect HIP1R-specific gene sets. Patients in the PD-1 inhibitor responder group had lower HIP1R expression by univariate logistic regression analysis (odds ratio (OR) = 0.235, p = 0.015) and multivariate logistic regression analysis (OR = 0.209, p = 0.014). Patients with high HIP1R expression had poorer progression-free survival (PFS) than patients with low HIP1R expression in univariate analysis (p = 0.037) and multivariate Cox analysis (hazard ratio = 2.098, p = 0.019). The web-based mRNA dataset also showed that high HIP1R expression correlated with inferior overall survival in lung adenocarcinoma (p = 0.026). GSEA revealed that HIP1R levels correlate with a set of genes that reflect PD-L1-related immune pathways. HIP1R expression may be a promising predictor for determination of patient responses to anti-PD-1 treatment.