Anoikis-associated genes as prognostic indicators in nasopharyngeal carcinoma: potential implications for the tumor immune microenvironment

Anoikis, a form of apoptosis induced by loss of cell-ECM interactions, is critical for preventing cancer metastasis. Resistance to anoikis enables tumor cells to survive and metastasize, contributing to poor outcomes. Nasopharyngeal carcinoma (NPC) is often diagnosed at advanced stages, limiting treatment options and increasing metastasis risk. This research explores the impact of anoikis-associated genes (ARGs) on the prognosis of nasopharyngeal carcinoma (NPC) and its tumor immune microenvironment, with the goal of uncovering potential targets for therapeutic intervention. Tissue samples from 212 NPC patients and RNA sequencing data from public datasets were analyzed to identify differentially expressed ARGs.A prognostic risk model was constructed through LASSO Cox regression, followed by validation via Kaplan–Meier survival analysis and the generation of receiver operating characteristic (ROC) curves to evaluate its predictive accuracy. To examine immune characteristics, CIBERSORT and xcell were utilized to assess both immune cell infiltration and the expression of immune checkpoint genes. Additionally, a drug sensitivity analysis was performed to determine potential effective treatments for patients in the high-risk category. A prognostic model featuring 16 anoikis-related genes (ARGs) indicated a lower progression-free survival rate for patients identified as high risk, with a satisfactory predictive performance (AUC > 0.7). High-risk tumors showed reduced infiltration by immune cells including CD8 + T cells, B cells, and NK cells, suggesting an immunosuppressive microenvironment. Downregulation of immune-related genes (GZMB, PRF1, CD79A) and MHC markers (HLA-A, TAP1) was observed, potentially affecting antigen presentation and immune activation. Drug sensitivity analysis highlighted Linsitinib and BIBF-1120 as potential treatments for high-risk patients, pending further validation of their efficacy and safety. Anoikis-related genes (ARGs) significantly influence the prognosis of nasopharyngeal carcinoma (NPC) by regulating immune responses. Targeting ARGs enhances immune function and improves outcomes in high-risk patients. Drug candidates interacting with ARGs may counteract treatment resistance in NPC.