Cellular senescence protein p16INK4a of cancer-associated fibroblasts (CAFs) as a prognostic indicator for cholangiocarcinoma patients

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Chayanit Piyawajanusorn
Suyanee Thongchot
Yingpinyapat Kittirat
Watcharin Loilome
Attapol Titapun
Nisana Namwat


Background and Objective: The tumor suppressor protein p16INK4a (inhibitor of CDK4/6) is a cyclin-dependent kinase inhibitor that plays an important role in cell cycle and cellular senescence. The senescent fibroblast expressing p16INK4a contributes to cancer development and poor prognosis of patients. Therefore, our approach focus on the expression of p16INK4a in cancer associated fibroblasts (CAFs) in cholangiocarcinoma (CCA) patient tissues and its clinicopathological correlation.

Method: The immunohistochemistry and immunofluorescence assays were used to investigate the expression of p16INK4a in forty six samples of CCA tissues. Pearson Chi-square test was used for analyzing of p16INK4a expression and clinicopathological data of CCA patients.

Result: Our results showed that high expression of p16INK4a protein was presented in CAFs surrounding tumor tissues of 24 cases (52.2%) of CCA patients. The positive expression of p16INK4a (p=0.041) was significantly associated with the non-papillary type.

Conclusion: The high expression of p16INK4a was found in CAFs, which referred to senescence-CAFs. Senescent-CAFs was significantly correlated with non-papillary type, which is the unfavorable feature of CCA patients.


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