NOS2 as a prognostic biomarker for early-onset colorectal cancer based on public data and clinical validation analysis

Early-onset colorectal cancer (EOCRC) was characterized by strong aggressiveness and high malignancy. The aim of this study was to screen suitable biomarkers for patients with EOCRC. EOCRC from The Cancer Genome Atlas Program (TCGA) database and Gene Expression Mapping (GEO) database were used to screen biomarkers for prognosis and treatment guidance. Clinical samples were used to verify the expression situation of these candidate biomarkers. The results showed the immune-related gene nitric oxide synthase 2 (NOS2) was independently associated with the poor prognosis of EOCRC patients in both TGCA and GEO database. The Immune Dysfunction and Exclusion (TIDE) analysis showed that multiple immunotherapy signatures, such as TIDE, Exclusion, and CAF, were difference among EOCRC patients with different risk scores, and significantly correlated with the expression of NOS2. Sensitivity analysis of chemotherapy drugs showed that NOS2 was significantly correlated with several chemotherapy drugs, such as MG.132_1862, BMS.754807_2171, and GEN.317_1926. Clinical validation analysis showed that the expression of NOS2 and its related genes CXCL1 and CXCL2 were significantly decreased in EOCRC patients. The results suggested that NOS2 can be used as a potential biomarker for EOCRC, which can be used for prognosis and guidance of immunotherapy and chemotherapy.