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. 2021 Jun;12(3):1132-1140.
doi: 10.21037/jgo-21-251.

The landscape of PD-L1 expression and somatic mutations in hepatocellular carcinoma

Hao Xu  1 , Xiao-Lu Liang  1 , Xiao-Guang Liu  1 , Nian-Ping Chen  1
Affiliations

The landscape of PD-L1 expression and somatic mutations in hepatocellular carcinoma

Hao Xu et al. J Gastrointest Oncol. 2021 Jun.

Abstract

Background: Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver, and becoming the third-leading cause of cancer-related mortality worldwide. Despite the immune checkpoint inhibitors and molecular targeted therapies have shown preferable efficacy in HCC, large number of HCC patients do not respond effectively to anti-PD-1 reagents. Besides, the accumulation of genetic mutations in cancer cells may lead to the therapy resistant. Hence, there are clinical gaps between genetic and transcriptomic biomarkers for the HCC treatment.

Methods: To investigate the genetic mapping of liver cancer, targeted deep sequencing (TDS) and bioinformatics analysis were performed on hepatocellular carcinoma (HCC) tumor tissues and matched blood samples. Furthermore, copy number variants (CNVs) and Tumor mutation burden (TMB) were calculated. Immunohistochemistry was applied to determine the PD-L1 expression in HCC tumor tissues. Clinical characteristic, PD-L1 expression, and the TMB were analyzed in 32 HCC patients.

Results: This study indicated that the PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group, and PD-L1 positive patients were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients. We also verified the top 30 mutated genes, including TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1, in our dataset. Our results indicated that PD-L1 positive patients possessed more tumors with vascular invasion and advanced CCLC stage. Moreover, PD-L1 positive patients exhibited a lower TMB compared to the PD-L1 negative group.

Conclusions: These findings could improve our understanding of the effects of immune checkpoint therapies on prognosis, and could facilitate the monitoring of somatic mutations in HCC.

Keywords: PD-L1; hepatocellular carcinoma; mutation landscape; targeted gene sequencing; tumor mutational burden (TMB).

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-251). The authors report that this work was sponsored by the Shanghai Tongshu Biotechnology Co., Ltd. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
PD-L1 expression in HCC tissue samples. (A) PD-L1 immunohistochemistry of Liujinxiang HCC biopsy. (B) HE staining of Liujinxiang HCC biopsy. (C) PD-L1 immunohistochemistry of Linjun HCC biopsy. (D) HE staining of Linjun HCC biopsy. (E) PD-L1 immunohistochemistry of Wangjiatuan HCC biopsy. (F) HE staining of a representative HCC biopsy. HCC, hepatocellular carcinoma. Scale bars =200 µm.
Figure 2
Figure 2
Correlation between PD-1 expression and the TMB. TMB, tumor mutational burden.
Figure 3
Figure 3
The Oncoprint of the top 30 driver genes in 46 HCC samples. HCC, hepatocellular carcinoma.
Figure 4
Figure 4
Landscape of somatic mutations of driver genes in HCC. (A) Classification of variant; (B) number of variants; (C) SNV class; (D) number of variants; (D) variants per sample; (E) variant classification summary; (F) top 10 mutated genes. HCC, hepatocellular carcinoma.
Figure 5
Figure 5
Significant mutated gene and signature distribution. (A) Significant mutated gene of HCC samples; (B) catalogue of somatic mutations of 46 HCC samples according to COSMIC. HCC, hepatocellular carcinoma; COSMIC, Catalogue of Somatic Mutations in Cancer.
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