CCNJL as a Prognostic Biomarker and Therapeutic Target in Cholangiocarcinoma

Introduction: Cholangiocarcinoma (CHOL) is a highly aggressive and lethal malignancy whose global incidence is increasing. This increase has been attributed to various factors, including an aging population and changes in environmental exposure. Therefore, the identification of reliable biomarkers for prognosis and treatment is crucial because of its poor survival rates and limited therapeutic options. This research examines the expression patterns and clinical relevance of Cyclin J Like (CCNJL) in CHOL, evaluating its potential as a candidate prognostic marker and immunotherapy target. materials and methods: We analyzed CCNJL expression in CHOL tissues compared to normal tissues using data from The Cancer Genome Atlas (TCGA) and the GSE31370 dataset. Differential expression analysis, Kaplan-Meier survival analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) were conducted to elucidate the relationships between CCNJL expression and clinical outcomes, immune infiltration, and drug sensitivity. The expression levels of CCNJL were confirmed in CHOL cell lines through quantitative reverse transcription PCR (qRT-PCR). Methods: We analyzed CCNJL expression in CHOL tissues compared with normal tissues using data from The Cancer Genome Atlas (TCGA) and the GSE31370 dataset. We performed differential expression analysis, Kaplan-Meier survival analysis, Cox regression analysis, and Gene Set Enrichment Analysis (GSEA) to elucidate relationships among CCNJL expression, clinical outcomes, immune infiltration, and drug sensitivity. CCNJL expression levels were validated in CHOL cell lines by quantitative real-time PCR (qRT-PCR). Results: CCNJL expression is significantly higher in CHOL tissues than in controls (mean ± SD: 1.714 ± 0.201 vs 0.165 ± 0.027; p < 0.001; AUC = 0.946). High CCNJL expression independently predicts worse overall survival (HR = 2.84, 95% CI = 1.01-7.95, p = 0.047) and disease-specific survival (HR = 3.40, 95% CI = 1.09-10.55, p = 0.035). GSEA linked high CCNJL expression to cytokine-cytokine receptor interaction, chemokine signaling, CAMs, and antigen processing. High CCNJL expression correlated inversely with CD8+ T-cell infiltration (p < 0.001) and with reduced sensitivity to elesclomol, tanespimycin, and selumetinib (all p < 0.05). qRT-PCR confirmed significant CCNJL up-regulation in CHOL cell lines. Discussion: CCNJL emerges as a novel, independent prognostic biomarker and a candidate immunotherapy target in CHOL. Its association with immune evasion and drug resistance suggests that therapeutic targeting of CCNJL could enhance antitumor immunity and restore drug sensitivity. Limitations include a modest sample size and a lack of functional validation; prospective multicenter studies and mechanistic investigations are warranted. Conclusion: CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts.