Positive Expression of Programmed Death Ligand 1 in Peritumoral Liver Tissue is Associated with Poor Survival after Curative Resection of Hepatocellular Carcinoma

Xiaomeng Dai; Jun Xue; Jianli Hu; Sheng-Li Yang; George G Chen; Paul B S Lai; Chao Yu; Cui Zeng; Xiefan Fang; Xiaoli Pan; Tao Zhang

doi:10.1016/j.tranon.2017.03.009

Positive Expression of Programmed Death Ligand 1 in Peritumoral Liver Tissue is Associated with Poor Survival after Curative Resection of Hepatocellular Carcinoma

Transl Oncol. 2017 Aug;10(4):511-517. doi: 10.1016/j.tranon.2017.03.009. Epub 2017 May 27.

Authors

Xiaomeng Dai¹, Jun Xue¹, Jianli Hu¹, Sheng-Li Yang², George G Chen³, Paul B S Lai³, Chao Yu⁴, Cui Zeng⁵, Xiefan Fang⁶, Xiaoli Pan⁷, Tao Zhang⁸

Affiliations

¹ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
² Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: jixufendou2013@gmail.com.
³ Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, NT, Hong Kong, China.
⁴ Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, PR China.
⁵ Division of Gastroenterology, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, China.
⁶ Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
⁷ Department of Gastroenterology and Hepatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
⁸ Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: taozhang66@outlook.com.

Abstract

Background: Recurrence or metastasis of hepatocellular carcinoma (HCC) is mainly intrahepatic after curative resection, demonstrating that the peritumoral environment is important but often neglected. Programmed death ligand 1 (PD-L1) in intratumoral liver tissues is a poor prognosis factor whose impact is removed after curative resection. However, PD-L1 expression remains in the peritumoral liver tissues and its distribution and prognostic value are still not clear.

Methods: We assessed the expression of PD-L1 by immunohistochemistry in peritumoral liver tissues from 90 HCC patients who underwent curative hepatectomy. The results were validated in an independent cohort of additional 90 HCC patients.

Results: We found PD-L1 positive expression in 31.11% (28/90) of peritumoral tissues. Peritumoral PD-L1 expression was associated with a significantly worse overall survival (OS) (P=.000) and disease-free survival (DFS) (P=.001) compared to the negative expression group. Additionally, peritumoral PD-L1 positivity significantly correlated with vascular invasion and a lower albumin level (≤35 g/L). Univariate and multivariate Cox regression models both revealed peritumoral PD-L1 as an independent prognostic factor for OS (HR=2.853, P=.002) and DFS (HR=2.362, P=.003). The prognostic value of PD-L1 positivity was validated in the independent data set.

Conclusions: Our data suggest PD-L1 expression in peritumoral hepatocytes is an independent prognostic factor for OS and DFS. This implies that future anti-cancer therapy should target not only residual tumor cells but also the "soil" for promoting tumor growth. Peritumoral PD-L1 could be a good target for adjuvant therapy after hepatectomy.