Decreased expression of PTH1R is a poor prognosis in hepatocellular carcinoma

Article type: Research Article

Authors: Wang, Hui-Ju^{a; b; 1} | Wang, Liang^{c; 1} | Song, Shu-Shu^d | He, Xiang-Lei^e | Pan, Hong-Ying^a | Hu, Zhi-Ming^{a; f; *} | Mou, Xiao-Zhou^{a; d; *}

Affiliations: [a] Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China | [b] Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou 310014, Zhejiang, China | [c] Department of Hand and Reconstruction Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China | [d] College of Life Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China | [e] Department of Pathology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China | [f] Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China

Correspondence: [*] Corresponding authors: Zhi-Ming Hu and Xiao-Zhou Mou, Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang, China. Tel.: +86 571 85893009; Fax: +86 571 85893009; E-mail: huzhiming4199@163.com,Tel.:+8657185893781;Fax:+8657185893781;E-mail:mouxz@zju.edu.cn.

Note: [1] These authors contributed equally.

Abstract: BACKGROUND AND AIM: Hypercalcemia is a potentially fatal and not rare complication of hepatocellular carcinoma (HCC), and its underlying mechanism remains unclear. Parathyroid hormone (PTH) is the most important regulator of the concentrations of calcium and phosphate in blood; parathyroid hormone-related protein (PTHrP) was the most frequent cause of humoral hypercalcemia of malignancy; parathyroid hormone 1 receptor (PTH1R) is the common receptor for PTH and PTHrP. The aim of this study is to investigate the expression of PTH, PTHrP, and PTH1R in HCC tissues, and their relationship with clinical pathological characters in HCC. METHODS: First, a meta-analysis based on online Oncomine Expression Array database was conducted to compare the different mRNA expression of PTH1R, PTH and PTHrP between hepatocellular carcinoma and normal tissues. Then, the protein expression level of differentially expressed gene was examined by immunohistochemistry staining in 223 HCC tissues and 102 non-tumorous liver tissues controls. The relationship between the protein expression and clinicopathological parameters was analyzed by χ2 test, and overall survival analysis was performed using Kaplan-Meier survival analysis. RESULTS: PTH1R mRNA expression was significantly lower in HCC tissues compared with normal tissues, while the expression of PTH and PTHrP showed no significant difference between HCC tissues and normal tissues. High PTH1R protein expression was found in 90/102 cases of adjacent non-tumorous liver tissues, and in 91 of 223 cases of HCC tissues. PTH1R expression was significantly related to tumor size, Edmondson Grade, AFP, and overall survival. CONCLUSIONS: PTH1R may be the major cause of hypercalcemia in HCC, and the decreased PTH1R expression was a poor prognosis in HCC.

Keywords: PTH1R, PTH, PTHrP, hepatocellular carcinoma

DOI: 10.3233/CBM-170823

Journal: Cancer Biomarkers, vol. 21, no. 3, pp. 723-730, 2018