Background: The mismatch repair (MMR) system prevents DNA mutation; therefore, deficient MMR protein (dMMR) expression causes genetic alterations and microsatellite instability (MSI). dMMR is correlated with a good outcome and treatment response in various cancers; however, the situation remains ambiguous in cholangiocarcinoma (CCA). This study aims to evaluate the prevalence of dMMR and investigate the correlation with clinicopathological features and the survival of CCA patients after resection. Materials and Methods: Serum and tissues were collected from CCA patients who underwent resection from January 2005 to December 2017. Serum OV IgG was examined using ELISA. The expression of MMR proteins MLH1, MSH2, MSH6 and PMS2 was investigated by immunohistochemistry; subsequently, MMR assessment was evaluated as either proficient or as deficient by pathologists. The clinicopathological features and MMR status were compared using the Chi-square test. Univariate and multivariate analyses were conducted to identify prognostic factors. Results: Among the 102 CCA patients, dMMR was detected in 22.5%. Survival analysis revealed that dMMR patients had better survival than pMMR (HR = 0.50, p = 0.008). In multivariate analysis, dMMR was an independent factor for a good prognosis in CCA patients (HR = 0.58, p = 0.041), especially at an early stage (HR = 0.18, p = 0.027). Moreover, subgroup analysis showed dMMR patients who received adjuvant chemotherapy had better survival than surgery alone (HR = 0.28, p = 0.012). Conclusion: This study showed a high prevalence of dMMR in cholangiocarcinoma with dMMR being the independent prognostic factor for good survival, especially in early-stage CCA and for patients who received adjuvant chemotherapy. dMMR should be the marker for selecting patients to receive a specific adjuvant treatment after resection for CCA.

Budding Uninhibited by Benzimidazole-Related 1 (BubR1) or BUB1 Mitotic Checkpoint Serine/Threonine Kinase B (BUB1B) is an essential component of the spindle assembly checkpoint (SAC), which controls chromosome separation during mitosis. Overexpression of BubR1 has been associated with the progression of various cancers. This study demonstrated that high expression of BubR1 correlated with cholangiocarcinogenesis in a hamster cholangiocarcinoma (CCA) model and was associated with shorter survival in patients with CCA. Co-expression of BubR1 and MPS1, which is a SAC-related protein, indicated a shorter survival rate in patients with CCA. Knockdown of BubR1 expression by specific siRNA (siBubR1) significantly decreased cell proliferation and colony formation while inducing apoptosis in CCA cell lines. In addition, suppression of BubR1 inhibited migration and invasion abilities via epithelial–mesenchymal transition (EMT). A combination of siBubR1 and chemotherapeutic drugs showed synergistic effects in CCA cell lines. Taken together, this finding suggested that BubR1 had oncogenic functions, which influenced CCA progression. Suppression of BubR1 might be an alternative option for CCA treatment.

Background: Preoperative inflammatory and nutrition-related markers—including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and controlling nutritional status (CONUT) score—have shown prognostic relevance in various malignancies. However, their comparative utility in predicting recurrence and survival across clinically relevant subgroups in patients with intrahepatic cholangiocarcinoma (iCCA) undergoing curative-intent resection remains unclear. Methods: This retrospective study included 213 patients with histologically confirmed iCCA who underwent curative-intent resection between 2015 and 2021. Preoperative NLR, LMR, PNI, and CONUT scores were calculated from laboratory data obtained within one week before resection. Clinicopathological variables, recurrence, and survival outcomes were analyzed using Cox regression and Kaplan–Meier methods. Results: A preoperative NLR ≥ 2.4 was independently associated with poorer DFS (HR = 1.66, p = 0.025) and OS (HR = 1.94, p = 0.006). This effect remained significant in patients with R0 resection (DFS: HR = 1.66, p = 0.004; OS: HR = 2.11, p = 0.014) and in those who subsequently developed recurrence (OS: HR = 1.83, p = 0.004). The CONUT score was correlated with OS in both R0 and recurrent subgroups. Tumor morphology, consistent with prior reports, was identified as a postoperative pathological factor associated with worse prognosis. Conclusions: Preoperative NLR was associated with poorer DFS and OS in iCCA patients undergoing curative-intent resection. This association was consistently observed in subgroups with R0 resection and in those who developed recurrence. Meanwhile, the CONUT score showed limited independent significance only among patients with R0 resection who experienced recurrence.

Cholangiocarcinoma (CCA) is a malignancy of the bile duct epithelium. The major problems of this cancer are late diagnosis and a high rate of metastasis. CCA patients in advanced stages have poor survival and cannot be cured with surgery. Therefore, targeting molecules involved in the metastatic process may be an effective CCA treatment. Monopolar spindle 1 (MPS1) is a kinase protein that controls the spindle assemble checkpoint in mitosis. It is overexpressed in proliferating cells and various cancers. The functional roles of MPS1 in CCA progression have not been investigated. The aims of this study were to examine the roles and molecular mechanisms of MPS1 in CCA progression. Immunohistochemistry results showed that MPS1 was up-regulated in carcinogenesis of CCA in a hamster model, and positive expression of MPS1 in human CCA tissues was correlated to short survival of CCA patients (n = 185). Small interfering RNA (siRNA)-induced knockdown of MPS1 expression reduced cell proliferation via G2/M arrest, colony formation, migration, and invasion. Moreover, MPS1 controlled epithelial to mesenchymal transition (EMT)-mediated migration via AKT and STAT3 signaling transductions. MPS1 was also involved in MMPs-dependent invasion of CCA cell lines. The current research highlights for the first time that MPS1 has an essential role in promoting the progression of CCA via AKT and STAT3 signaling pathways and could be an attractive target for metastatic CCA treatment.

Background/Objectives: Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is a frequent but insufficiently studied complication in cholangiocarcinoma (CCA). This study aimed to evaluate incidence and risk factors of PEP in CCA. Methods: We retrospectively reviewed 148 CCA patients who underwent ERCP between 2019 and 2022. Demographic, clinical, and procedural data were compared between patients with and without PEP, and logistic regression was used to identify independent predictors. Results: PEP occurred in 26.4% of patients, mostly aged ≥ 66 years, male, and with perihilar CCA. In PEP cases, metallic stents were frequently used, procedures often exceeded 60 min, and 28.2% developed post-ERCP cholangitis. Hospital stay was ≥4 days in nearly 90% of cases. PEP severity was mild (10.3%), moderate (61.5%), and severe (28.2%). Multivariate analysis showed older age, metallic stent placement, and post-ERCP cholangitis as independent risk factors, while bilirubin ≥ 15 mg/dL was protective. Conclusions: PEP occurred in over one-fourth of CCA patients, predominantly of moderate severity. Independent risk factors included older age, metallic stent placement, and post-ERCP cholangitis, whereas bilirubin ≥ 15 mg/dL was protective. Awareness of these factors may aid risk stratification and prevention in this high-risk group.

Background: Cholangiocarcinoma (CCA) has the highest incidence in Northeastern Thailand, where patients generally present with late diagnosis and poor prognosis. Opisthorchis viverrini (OV) infection is the major cause of CCA, with oxidative stress driving DNA mutations and genetic instability. Microsatellite instability (MSI) is a predictive biomarker in several cancers. This study aimed to investigate MSI status and its association with clinicopathological features and survival of CCA patients. Methods: Tissue and serum samples were collected from 25 surgical CCA patients. MSI status and mismatch repair (MMR) proteins were evaluated using an MSI scanner and immunohistochemistry (IHC). Serum OV IgG was assessed by ELISA, while tumor-infiltrating lymphocytes (TILs) were evaluated by two pathologists. Associations of MSI with clinicopathological features, OV status, MMR, and survival were analyzed. Results: Among CCA patients, 66.7% were MSI-high and 33.3% were MSI-low. MSI-high significantly correlated with age < 57 years, intraductal growth pattern, OV positivity, and early-stage disease. Patients with MSI-high and high TILs showed markedly improved median survival compared to MSI-low with low TILs (94.0 vs. 16.8 and 3.0 months; HR = 6.82 and 14.10; p = 0.004 and 0.001). Incorporation of MSI and TILs remained an independent prognostic factor in multivariate analysis (p < 0.05). Conclusions: MSI-high is highly prevalent in OV-associated CCA and is associated with intraductal growth, OV infection, and early-stage disease. Combined MSI and TIL status may serve as an independent prognostic factor, warranting validation in larger cohorts.