whole-exome sequencing identifies a set of genes as markers of early hepatocellular carcinoma recurrence

作者：Shichun Lu, Huizhong Shi, Wenwen Zhang, Bingyang Hu, Yafei Wang, Ze Zhang, Guankun Mao, Chonghui Li, Ying Sun · 发表于：Research Square · 年份：2022 · DOI：10.21203/rs.3.rs-2033879/v1 · 研究领域：Glycosylation and Glycoproteins Research、Ferroptosis and cancer prognosis、Hepatocellular Carcinoma Treatment and Prognosis

Abstract BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by a high recurrence rate and poor prognosis. In recent years, the therapeutic regimen of PD-1 antibody combined with multi-targeted tyrosine kinase inhibitors (mTKIs) has achieved better results in the clinical application of hepatocellular carcinoma. Whole-exome sequencing can reflect the mutational characteristics of patients’ exons and guide the clinical selection of molecular targeting drugs more accurately, which is in line with the concept of precision medicine. METHODS: We performed exome sequencing on 63 patients with HCC treated with radical surgery at our hospital and collected their clinical indexes and postoperative follow-up data. Using machine learning, a prediction model for recurrence within one year was constructed and the model was presented in a nomogram. Patients treated with PD-1 antibodies in combination with mTKIs after relapse were grouped by prognosis, and the valuable mutated genes were screened according to whole-exome sequencing data. The tumor tissue immune cells were analyzed using the UCSC Xena database. The expressions of target proteins were verified by Polymerase Chain Reaction (PCR) and Immunohistochemistry (IHC) respectively on commercial HCC cell lines and pathological specimens of hepatocellular carcinoma collected clinically. RESULTS: The proportion of patients who relapsed within a year was 41% and the prognosis of those patients was poor. The characteristic exon muta...