Labyrinthin Expression Is Associated with Poor Prognosis in Patients with Non-Small-Cell Lung Cancer

SIMPLE SUMMARY: Adenocarcinomas represent nearly 40% of all cancer types, and account for more than 70% of cancer-related deaths. Labyrinthin (LAB) is a novel cancer neoantigen expressed on the surface of adenocarcinoma cells of various cancer types. Several treatment strategies are being developed for targeting LAB as a pan-adenocarcinoma target. This study aimed to develop an immunohistochemistry (IHC) assay to detect LAB expression on archival tumor specimens of non-small-cell lung cancer (NSCLC) and characterize the clinical significance of LAB expression. We also explored LAB mRNA expression by RNA sequencing using NSCLC data in The Cancer Genome Atlas (TCGA), and correlated with clinical phenotype and outcome. Further study is warranted to validate LAB IHC and LAB RNA expression as independent biomarkers for selecting patients for cancer therapy targeting LAB. ABSTRACT: To determine Labyrinthin (LAB) expression in non-small-cell lung cancer (NSCLC), we immunostained and scored for LAB immunohistochemistry (IHC) expression on sections of tissue microarrays (TMAs) prepared from 256 archival tissue blocks of NSCLC. Propensity-score-weighted Kaplan–Meier curves and weighted Cox models were used to associate LAB expression with overall survival. LAB mRNA expression was assessed in The Cancer Genome Atlas (TCGA) and correlated with clinical phenotype and outcome. Positive LAB IHC expression (>5% of tumor cells) was detected in 208/256 (81.3%) of NSCLC samples, and found in both lung adenocarcinomas (LUAD) and lung squamous cell cancer (LUSC). LAB positivity was associated with poor overall survival (HR = 3.56, 95% CI: 2.3–5.4; p < 0.0001) and high tumor differentiation grade or metastasis compared with negative LAB expression. Univariant and multivariate survival analyses demonstrated LAB expression as an independent prognostic factor for NSCLC patients. LAB RNA expression in TCGA-LUAD was higher in primary and advanced-stage tumors than in normal tissue, and was associated with poorer overall survival. No significant differences or associations were found with LAB RNA expression in TCGA-LUSC. The LAB IHC assay is being used to identify candidate cancer patients for the first-in-human phase I trial evaluating the LAB vaccines (UCDCC#296, NCT051013560).