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| Home > Publications database > Prognostic significance of germline ARID5B and LEPR polymorphisms in intrahepatic and perihilar cholangiocarcinoma after curative resection |
| Home > Publications database > Prognostic significance of germline ARID5B and LEPR polymorphisms in intrahepatic and perihilar cholangiocarcinoma after curative resection |
| Journal Article | DKFZ-2026-01887 |
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2026
Beijing Baishideng BioMed Scientific Co.
Beijing
Abstract: BACKGROUND Cholangiocarcinoma (CCA) is a biologically heterogeneous and aggressive biliary malignancy associated with poor survival outcomes despite surgical resection. Germline genetic variants, including single-nucleotide polymorphisms (SNPs), may modulate tumor behavior and inform postoperative risk stratification. AIM To evaluate the prognostic relevance of selected tumor-related SNPs in patients with intrahepatic CCA (iCCA) and perihilar CCA (pCCA). METHODS In this single-centre retrospective cohort study, we genotyped eight SNPs in cancer-associated genes (ARID5B, LEPR, TERT, SH2B3, MMEL1, PROM1, HDAC7, RUNX3) in 229 patients (112 iCCA, 117 pCCA) who underwent curative-intent resection between 2009 and 2020. RESULTS Associations between SNPs and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were assessed using Kaplan-Meier analysis, univariate, and multivariate Cox regression models. The rs10740055 AA genotype in ARID5B was associated with significantly shorter RFS [hazard ratio (HR) = 1.87, P = 0.017], CSS (HR = 1.78, P = 0.033) and OS (HR = 1.79, P = 0.021) in iCCA as well as shorter RFS (HR = 1.84, P = 0.031), CSS (HR = 2.18, P = 0.005) and OS (HR = 1.84, P = 0.001) univariate analyses. However, only in iCCA did it retain significance in multivariate analysis alongside other important clinicopathological variables (RFS: HR = 2.41, P = 0.005; CSS: HR = 2.27, P = 0.020 and OS: HR = 4.10, P = 0.001). Further, the LEPR rs1137101 GG genotype was associated with significantly shorter RFS (HR = 1.91, P = 0.010). Germline variants in ARID5B and LEPR were associated with poorer prognosis following resection for CCA, with rs10740055 in ARID5B serving as an independent predictor of survival particularly in iCCA. CONCLUSION These findings support the potential utility of incorporating host genetic markers into postoperative prognostic models for CCA. Prospective validation and mechanistic studies are warranted.
; Allianz-Lizenz / DFG ; Clarivate Analytics Master Journal List ; Essential Science Indicators ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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