Expression of MUC16/CA125 Is Associated with Impaired Survival in Patients with Surgically Resected Cholangiocarcinoma

Abstract

MUC16/CA125 is associated with cancer proliferation in several tumor entities. The data on MUC16 expression in cholangiocarcinoma (CCA) tissue are very limited. The aim of this study was to assess the MUC16 status and its impact on survival in CCA patients. All the patients with surgically resected CCA that were diagnosed between August 2005 and December 2021 at the University Hospital Frankfurt were retrospectively analyzed. A 7-Mucin biomarker panel was assessed by immunohistochemistry. For overall survival (OS), Kaplan–Meier curves and Cox-regression analyses were performed. Randomly selected intrahepatic cholangiocarcinoma (iCCA) were further processed for differential expression profiling. A total of 168 patients with CCA were classified as MUC16 (−) (66%, n = 111) and MUC16 (+) (34%, n = 57). Subgroup analyses revealed a median OS of 56.1 months (95% CI = 42.4–69.9 months) and 27.4 months (95% CI = 15.8–39.1 months) for MUC16 (−) and MUC16 (+), respectively (p =< 0.001). In multivariate analysis, MUC16 (+) (HR = 1.6, 95% CI = 1–2.6, p = 0.032) was an independent risk factor for poor prognosis. Prominently deregulated pathways have been identified following MUC16 expression, overrepresented in cell cycle and immune system exhaustion processes. These findings suggest including MUC16 in clinical routine diagnostics as well as studying its molecular pathways to identify further mechanistic key players.

Active Autophagy Is Associated with Favorable Outcome in Patients with Surgically Resected Cholangiocarcinoma

“…Clinicopathological characteristics were compared between patients with and without active autophagy, while categorical and continuous variables were analyzed as indicated recently [27]. Definition and statistical analysis of overall survival (OS), including Kaplan-Meier curves and Cox regression analysis, was performed as previously described [27]. A significance level of p < 0.05 was used for determining statistical significance.…”

“…The study builds upon the patient population and data base of our previously established tissue microarray (TMA) cohort of CCA patients [27], while histological confirmation of SD-iCCA and LD-iCCA cases was confirmed as well [28]. The University Cancer Center Frankfurt (UCT) provided the tissue samples utilized in this study.…”

“…TMA construction was performed as previously reported [27]. Staining of LC3B (polyclonal; dilution: 1:500; incubation time: 30 min; NovusBio, Centennial, CO, USA), p62 (Clone: EP396; dilution: 1:200; incubation time: 30 min; Abcam, Cambridge, UK), Beclin-1 (monoclonal; dilution: 1:100; incubation time: 30 min; REF#AC-0276, Abcam, Cambridge, UK) and pan-acetylated-lysine (polyclonal; dilution: 1:1000; incubation time: 30 min; REF#9441, Cell Signaling Technology, Danvers, MA, USA) was conducted.…”

“…RNA isolation was conducted as described recently [27]. Immune-exhaustion expression analysis was performed using the Nanostring nCounter ® Platform, the Immune Exhaustion Panel v1, Nanostring nSolver™ software v4 as well as the nCounter ® Advanced Analysis module v2.0.115 (Nanostring, Seattle, WA, USA), as indicated previously [27]. iCCA patients were classified into two groups based on the presence or absence of active autophagy, as determined by prior IHC analysis.…”

“…Our previously established cohort of 23 cases of iCCA processed for gene expression profiling of immune-exhaustion gene sets was utilized for our autophagy approach in silico [27]. By means of the applied IHC scoring system, the cases were stratified into groups of active (6/23) and non-active autophagy (17/23) and analyzed to scrutinize expression changes.…”