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

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.

Metastatic Hepatocellular Carcinoma To The Nasal Cavity And Sinus: A Potential Diagnostic Challenge And The Detection Of Programmed Death Ligand-1 Expression

“…Nevertheless these ndings indicated a potential immunotherapy opportunities for advanced patients. Recently, research shows PD-L1 positive patients with HCC were more likely to suffer from aggressive clinicopathologic features than PD-L1 negative patients (30). We are not able to obtain the same results as to the sinonasal metastases.…”

Tumor Mutational Burden for Predicting Prognosis and Therapy Outcome of Hepatocellular Carcinoma

“…This CMG-related signature suggests this cluster of HCC patients could benefit from ICI therapy more than the high-risk one. An analysis of 32 primary HCC tissues collected from patients admitted to the Hospital of Guangdong between May 2019 and November 2020 revealed that PD-L1-positive patients had lower TMB, greater vascular invasion and more advanced BCLC stages than PD-L1-negative patients [ 44 ]. Moreover, among the 30 most mutated genes, this study identified TP53, CTNNB1, KMT2D, AXIN1, ALK, and NOTCH1.…”

The advanced development of molecular targeted therapy for hepatocellular carcinoma

“…Several studies have indicated that PD-L1 and TMB are independent predictors of the immune checkpoint blockade response, and PD-L1 expression and TMB have a low correlation across multiple tumor types, including HCC 86 – 88 . In contrast, Xu et al 89 have reported that PD-L1 positive patients exhibit a lower TMB than PD-L1 negative patients, and that PD-L1 positive patients are more likely to have aggressive clinicopathological features than PD-L1 negative patients. A model of 15 immune-associated gene pairs associated with TMB has been developed for prediction of prognosis 90 .…”