Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients

Liuxi Chen; Xingxing Huang; Wenzheng Zhang; Ying Liu; Bi Chen; Yu Xiang; Ruonan Zhang; Mingming Zhang; Jiao Feng; Shuiping Liu; Ting Duan; Xiaying Chen; Wengang Wang; Ting Pan; Lili Yan; Ting Jin; Guohua Li; Yongqiang Li; Tian Xie; Xinbing Sui

doi:10.7150/jca.46158

Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients

J Cancer. 2020 Jul 11;11(18):5440-5448. doi: 10.7150/jca.46158. eCollection 2020.

Authors

Liuxi Chen^{1

2}, Xingxing Huang^{1

2}, Wenzheng Zhang^{1

2}, Ying Liu^{1

2}, Bi Chen^{1

2

3}, Yu Xiang², Ruonan Zhang^{1

2

3}, Mingming Zhang², Jiao Feng², Shuiping Liu², Ting Duan², Xiaying Chen², Wengang Wang^{1

2}, Ting Pan², Lili Yan², Ting Jin², Guohua Li², Yongqiang Li¹, Tian Xie^{1

2

3}, Xinbing Sui^{1

2

3}

Affiliations

¹ Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China.
² Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, China.
³ State Key Laboratory of Quality Research in Chinese Medicines, Faculty of Chinese Medicine, Macau University of Science and Technology, Macau, P.R. China.

Abstract

Purpose: To investigate the correlation between the expression of PD-L1, SOCS3 and immune-related biomarkers CD276, CD4, CD8 in hepatocellular carcinoma (HCC) and further determine the relationship with clinicopathologic characteristics and the prognostic value of their co-expression in HCC patients. Methods: We assessed the expression of PD-L1, CD276, SOCS3, CD4 and CD8 by immunohistochemistry in tumor tissue from 74 HCC patients who underwent curative hepatectomy. Results: High expression of PD-L1 was significantly associated with high Edmondson grade (p<0.01) and elevated enzyme (p=0.037); high expression of CD276 was significantly correlated with high Edmondson grade (p=0.021); high expression of SOCS3 was significantly associated with age (p=0.026) and tumor size (p=0.041), while PD-L1 showed no significant correlation. The expression of PD-L1, CD276, SOCS3 protein and other clinicopathological factors (sex, vascular invasion, tumor number, tumor capsule, pT stage, liver cirrhosis, HBsAg, TBiL, AFP) showed no significant correlation (p>0.05). High expression of CD8 was respectively significantly associated with worse overall survival (OS) (p=0.002). There was no significantly difference between CD4 and CD8 high-expression and overall survival (OS) (p=0.100). Both high expression of PD-L1 (p=0.003) and low expression of SOCS3 (p=0.015) was significantly associated with worse overall survival (OS). But CD276 only had a trendency (p=0.166). Additionally, multivariate Cox regression models implied that PD-L1, SOCS3, as well as both CD4 and CD8 was an independent prognostic factor for OS (p<0.05). Furthermore, HCC patients with PD-L1 low-expression and SOCS3 high-expression had a better prognostic according to the different pT stages (p<0.05). Conclusions: We for the first time demonstrated that PD-L1 and SOCS3 were independent prognostic factor for HCC patients. Co-expression of low PD-L1 and high SOCS3 could be a better predictive marker for HCC patients.

Keywords: CD276; CD4; CD8; PD-L1; SOCS3; hepatocellular carcinoma; prognostic value.