Cancer progression involves dynamic crosstalk between tumor-intrinsic pathways and microenvironmental remodeling, and identifying pan-cancer biomarkers is critical for precision oncology. CDKN2AIPNL exhibits a paradoxical role in cancer, acting as a tumor suppressor in myeloid malignancies but promoting solid tumor progression, yet its systematic pan-cancer characteristics remain unelucidated. This study aimed to comprehensively analyze CDKN2AIPNL’s expression patterns, prognostic value, genetic alterations, and molecular mechanisms across multiple tumor types using public datasets including TCGA, GTEx, HPA, and tools such as GEPIA2, cBioPortal, TIMER2, STRING, and BioGRID. We performed expression difference analysis, survival analysis (overall survival, disease-free survival, progression-free survival), genetic alteration analysis, cancer-associated fibroblast (CAF) infiltration analysis, and gene/protein interaction enrichment analysis. Results showed that CDKN2AIPNL was significantly upregulated in multiple tumors (e.g., LIHC, UVM, BRCA, LUAD) and downregulated in others (e.g., KICH, KIRP, THCA), with high tumor specificity. Elevated CDKN2AIPNL expression correlated with poor overall survival in LIHC (HR = 1.7, p = 0.0026), UVM (HR = 26, p = 2.2e-6), BRCA (HR = 26, p = 2.2e-6), LUAD (HR = 1.36, p = 0.049), PCPG (HR = 1.71, p = 0.0012), and TGCT (HR = 0.37, p=0.023), and was associated with advanced tumor stages in metabolically active cancers. Genetic alterations (amplifications and mutations) were frequent in KIRC (>5%) and ACC (>4%), with all mutations localized to the XTBD region, and amplification predicted poor prognosis in PRAD (p = 0.008) while mutations conferred favorable outcomes in BLCA. CDKN2AIPNL expression positively correlated with CAF infiltration in ESCA, KICH, UVM, and other tumors, and interacted with MYC, XRN2, and CHAMP1 to regulate metabolic reprogramming, cell cycle, and immune suppression. Our findings systematically reveal CDKN2AIPNL’s dual role in tumorigenesis and validate it as a potential pan-cancer prognostic biomarker, providing novel insights for cancer diagnosis and targeted therapy.
Yuan et al. (Thu,) studied this question.