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

Research Paper

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

Liuxi Chen1,2*, Xingxing Huang1,2*, Wenzheng Zhang1,2, Ying Liu1,2, Bi Chen1,2,3, Yu Xiang2, Ruonan Zhang1,2,3, Mingming Zhang2, Jiao Feng2, Shuiping Liu2, Ting Duan2, Xiaying Chen2, Wengang Wang1,2, Ting Pan2, Lili Yan2, Ting Jin2, Guohua Li2, Yongqiang Li1✉, Tian Xie1,2,3✉, Xinbing Sui1,2,3✉

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.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Chen L, Huang X, Zhang W, Liu Y, Chen B, Xiang Y, Zhang R, Zhang M, Feng J, Liu S, Duan T, Chen X, Wang W, Pan T, Yan L, Jin T, Li G, Li Y, Xie T, Sui X. Correlation of PD-L1 and SOCS3 Co-expression with the Prognosis of Hepatocellular Carcinoma Patients. J Cancer 2020; 11(18):5440-5448. doi:10.7150/jca.46158. Available from https://www.jcancer.org/v11p5440.htm

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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: PD-L1, SOCS3, CD276, CD4, CD8, hepatocellular carcinoma, prognostic value