High level of CD73 predicts poor prognosis of intrahepatic cholangiocarcinoma

Ya-Ping Xu; Ying-Qun Zhou; Yu-Jie Zhao; Yan Zhao; Feng Wang; Xiao-Yong Huang; Chuan-Yong Guo

doi:10.7150/jca.51038

High level of CD73 predicts poor prognosis of intrahepatic cholangiocarcinoma

J Cancer. 2021 Jun 4;12(15):4655-4660. doi: 10.7150/jca.51038. eCollection 2021.

Authors

Ya-Ping Xu^{1

2}, Ying-Qun Zhou², Yu-Jie Zhao², Yan Zhao², Feng Wang², Xiao-Yong Huang³, Chuan-Yong Guo^{1

2}

Affiliations

¹ Department of Gastroenterology, Shanghai Tenth people's hospital, School of Clinical Medicine of Nanjing Medical University, Shanghai, 200072, P.R. China.
² Department of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
³ Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai 200032, P.R. China.

Abstract

Background: Despite recent improvements in the diagnosis and therapy of intrahepatic cholangiocarcinoma (ICC), the prognosis for ICC patients remains poor. Therefore, it is needed to identify new biological indicators for ICC progression. Methods: Immunohistochemistry was engaged to inspect the ecto-5'-nucleotidase (CD73) and CD8 expressions in tissue microarrays including tissues from 140 ICC patients. Then, the association between the level of CD73/CD8 and clinicopathologic characteristics of ICC was analysed. Finally, the prognostic value of CD73 and CD8 levels in ICC patients was assessed by Kaplan-Meier and multivariate and univariate analyses. Results: The CD73 expression was evidently upregulated in ICC tissues compared to the corresponding peritumoral tissues. The elevated CD73 expression was positively related to the lymphatic metastasis (p=0.049). While the level of tumour-infiltrating CD8 T⁺ cells in tumour tissues was negatively associated with serum AFP (p=0.019), tumor size (p=0.028), and lymphatic metastasis (p=0.039). Additionally, patients with elevated CD73 expression or low tumour-infiltrating CD8⁺ T cells exhibited shorter overall survival (OS) and higher disease-free survival (DFS) rates than patients with low CD73 expression and/or high tumour-infiltrating CD8⁺ T cells. Notably, the overexpression of CD73 or low tumour-infiltrating CD8⁺ T cells was an independent indicator for predicting the OS and DFS of ICC patients. Conclusions: We revealed that CD73 expression and low tumour-infiltrating CD8⁺T cells are valuable predictors of survival and recurrence in patients with ICC.

Keywords: CD73; CD8; intrahepatic cholangiocarcinoma; prognosis.