Identification of SCO1 as a Cuproptosis-Associated Prognostic Biomarker and Its Correlation with Immune Checkpoints in Cholangiocarcinoma

Cholangiocarcinoma (CHOL) represents an aggressive biliary malignancy with limited therapeutic alternatives and extremely poor long-term survival outcomes. Cuproptosis, a newly discovered copper-triggered programmed cell death pathway, has been proven to interfere with tumor progression and intratumoral immune regulation, yet its clinical prognostic value in CHOL remains underexplored. In this work, we retrieved paired transcriptome sequencing data and corresponding clinical follow-up records of CHOL patients stored in the TCGA database. We first screened differentially expressed cuproptosis-related genes (CRGs) between tumor and normal bile duct tissues, followed by univariate Cox regression survival screening, Kaplan-Meier survival stratification, and time-dependent receiver operating characteristic (ROC) modeling. Spearman’s rank correlation analysis was further adopted to quantify the linear association between the target gene and classic immune checkpoint molecules. Among all 37 collected CRGs, 21 genes exhibited significant expression discrepancies in CHOL lesions. Subsequent survival screening singled out SCO1 as an independent risk indicator for overall survival (OS), with a hazard ratio of 2.847 and a 95% confidence interval ranging from 1.339 to 6.054 (P = 0.0066). Patients with elevated SCO1 expression displayed remarkably shortened survival time, and log-rank testing confirmed the statistical significance of survival divergence (P = 0.01). Time-dependent ROC curves revealed that SCO1 achieved favorable predictive power for short- and medium-term prognosis, with 1-year and 3-year AUC values reaching 0.706 and 0.731 respectively. Correlation analysis further demonstrated that SCO1 transcript abundance was negatively correlated with two core immune checkpoint genes, PDCD1 (r = −0.423, P = 0.004) and CTLA4 (r = −0.373, P = 0.012). Our analytical results verify that SCO1 can act as a novel prognostic marker for CHOL and is tightly associated with intratumoral immune checkpoint status, which offers new directions for subsequent clinical validation and immunotherapy research.