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

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

Xiaomeng Dai  1 , Jun Xue  1 , Jianli Hu  1 , Sheng-Li Yang  2 , George G Chen  3 , Paul B S Lai  3 , Chao Yu  4 , Cui Zeng  5 , Xiefan Fang  6 , Xiaoli Pan  7 , Tao Zhang  8
Affiliations

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

Xiaomeng Dai et al. Transl Oncol. 2017 Aug.

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.

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Figures

Figure 1.
Figure 1
Peritumoral positive hepatocellular cytoplasmic/membranous staining for PD-L1 in experimental group (A), and validation cohort (B).
Figure 2.
Figure 2
Prognostic values of peritumoral PD-L1 expression. Kaplan–Meier overall survival (OS) and disease-free survival (DFS) analysis in experimental cohort (A and B), and validation cohort (C and D), respectively, according to peritumoral PD-L1 expression.
See this image and copyright information in PMC

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