Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients

Bin Jia; Peiyi Xia; Junqiang Dong; Wenhao Feng; Wenjia Wang; Enjie Liu; Guozhong Jiang; Yanru Qin

doi:10.3389/fonc.2022.1086908

Genetic testing and prognosis of sarcomatoid hepatocellular carcinoma patients

Front Oncol. 2023 Jan 17:12:1086908. doi: 10.3389/fonc.2022.1086908. eCollection 2022.

Authors

Bin Jia¹, Peiyi Xia², Junqiang Dong³, Wenhao Feng¹, Wenjia Wang¹, Enjie Liu², Guozhong Jiang², Yanru Qin¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
² Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
³ Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Abstract

Background: Sarcomatoid hepatocellular carcinoma (SHC) is a rare epithelial malignancy with high invasiveness and poor prognosis. However, the molecular characteristics and main driver genes for SHC have not been determined. The aim of this study is to explore the potentially actionable mutations of driver genes, which may provide more therapeutic options for SHC.

Methods: In this study, DNA extraction and library preparation were performed using tumor tissues from 28 SHC patients. Then we used Miseq platform (Illumina) to sequence the target-enriched library, and we aligned and processed the sequencing data. The gene groups were tested for SNVs/Indels/CNVs. Tumor mutation burden (TMB) was assessed by the 425-cancer-relevant gene panel. Multivariate analysis of COX's model was used for survival analysis (OS) of patients' clinical characteristics.

Result: The median overall survival (OS) of the patients was only 4.4 months. TP53, TERT, and KRAS were the top three frequently mutated genes, with frequencies of 89.3%, 64.3%, and 21.4%, respectively. A considerable number of patients carried mutations in genes involved in the TP53 pathway (96%) and DNA Damage Repair (DDR) pathway (21%). Multiple potentially actionable mutations, such as NTRK1 fusions and BRCA1/2 mutations, were identified in SHCs.

Conclusions: This study shows a landscape of gene mutations in SHC. SHC has high mutation rates in TP53 pathway and DDR pathway. The potentially actionable mutations of driver genes may provide more therapeutic options for SHC. Survival analysis found that age, smoking, drinking, and tumor diameter may be independent prognostic predictors of SHC.

Keywords: gene mutation; genetic testing; hepatic tumors; prognosis; sarcomatoid carcinoma.

Grants and funding

This work was supported by grants from the Key Research and Development Project (No. 222102310069), the Key Research Project of Colleges and Universities (No. 20A320053) of Henan, grants from National Natural Science Foundation of China (No. 82172941) and Henan Province Medical Science and Technology Research Project (No. 212102310134).