Cdk5 as a possible new target in biliary tract cancer: preliminary in-situ findings

Objective Biliary tract cancer (BTC) still shows a poor survival prognosis dueto the lack of sufficient therapies and the observed chemoresistance. Cyclin-dependent kinases (Cdks) have gained increasing interest as potential cancertherapeutic targets in the last few years. The current study evaluates the proteinexpression of Cdk5 and its biomarker potency in a clinico-pathologicallywell-characterized patient cohort of BTCs.

Methods For this study, a comprehensive cohort of resected human BTC specimen (n=119) was retrospectively evaluated. The immunohistochemical scoresof Cdk5 (including intensity and extensity) in the tumor centre and margin wererelated to clinico-pathological characteristics as well as to markers (E-cadherinand vimentin) of epithelial-mesenchymal differentiation (EMT).

Results The patient cohort consists of mostly intrahepatic BTC (n=58 (48.7 %) with mass forming (n = 56 (47.1 %) or periductal growth (n=59 (49.6) pattern, mostly low grade differentiation (n=75 (63 %)) and homogenous distribution of UICC stages (I-II: n = 62 (52.1 %); III-IV: n=57 (47.9 %). Cdk5 was differentially more expressed at the tumor centre (mean (confidence interval) 40.1 (30.3-50.0)/median (min-max) 10.0 (0/250)) compared to the tumor margin (23.5(16.2-30.7 / 6.6 (0-230). Furthermore, the statistical analysis revealed an association of the expression pattern of Cdk5 with clinico-pathological parameters (including overall survival) and markers of EMT.

Conclusion and Outlook Our preliminary data show (i) that Cdk5 is generally expressed in BTC using immunohistochemistry and (ii) that protein expression of Cdk5 correlates with clinic-pathological characteristics including prognostic aspects, Therefore, in future experiments, we will evaluate cellular and molecular effects of pharmacological Cdk5 inhibition on BTC cells.

Publication History

Article published online:
26 January 2022