ADAM10 as a Potential Biomarker in Non-Small Cell Lung Cancer and Its Major Histologic Subtypes

Background and Objectives: A disintegrin and metalloproteinase 10 (ADAM10) is a membrane-anchored metalloprotease involved in ectodomain shedding and cancer progression. However, its molecular and prognostic significance across major histological subtypes of non-small cell lung cancer (NSCLC) remains unclear. This study evaluated the clinical and molecular relevance of ADAM10 in NSCLC, focusing on lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Materials and Methods: Transcriptomic and clinicopathological data from 980 patients with NSCLC, including 491 patients with LUAD and 489 patients with LUSC, were obtained from The Cancer Genome Atlas through the OncoLnc database. Patients in each cohort were classified into ADAM10-high and ADAM10-low groups according to the median ADAM10 mRNA expression level. Univariate and multivariate Cox proportional hazards regression analyses were performed to evaluate the prognostic significance of ADAM10 expression. Results: ADAM10 expression was not significantly associated with baseline clinicopathological characteristics in the overall cohort or within the LUAD and LUSC subgroups. However, ADAM10 expression showed distinct molecular associations according to histologic subtype. In LUAD, ADAM10 expression was positively correlated with KRAS expression (ρ = 0.286, p < 0.001), BRAF expression (ρ = 0.145, p = 0.001), and EGFR expression (ρ = 0.187, p < 0.001), while it was negatively correlated with TP53 expression (ρ = -0.12, p = 0.005), whereas in LUSC, it was positively correlated with PIK3CA. High ADAM10 expression was associated with significantly poorer EFS and OS in the overall NSCLC cohort. In multivariate analyses, high ADAM10 expression remained an independent predictor of shorter EFS (HR = 1.352, 95% CI = 1.041-1.755, p = 0.024) and OS (HR = 1.335, 95% CI = 1.089-1.636, p = 0.005), independent of clinicopathological factors. Conclusions: High ADAM10 expression was independently associated with poorer survival outcomes in NSCLC, with a more pronounced prognostic impact in LUAD than in LUSC. These findings suggest that ADAM10 may serve as a potential prognostic biomarker in NSCLC, particularly in LUAD.