Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world and the fourth most common cause of cancer-related death. Viral hepatitis is a common cause of liver cancer, and my country is precisely a country with hepatitis, and my country has a high burden of liver cancer. Although many studies are now focused on the genetic characteristics of liver cancer, the genetic profile of HCC patients in China has not yet been fully studied.
        This study aims to analyze the genetic characteristics of HCC patients in China.
        A total of 165 HCC patients were recruited, including 146 men and 19 women. The median age is 55 years (range 27-78 years). At the same time, the corresponding clinical and pathological information of the patients was collected. A total of 168 tumor tissues were collected for next-generation sequencing (NGS), covering 450 genes. Variations detected include single nucleotide variations (SNV), small and long insertions and deletions (InDels), copy number variations, and gene recombination. In addition, the tumor mutation burden (TMB) was also analyzed, and the highest quartile of HCC was classified as high TMB.
        A total of 1,004 genetic variants were detected in 258 genes in 168 HCC tissues. The TMB values of 160 HCC samples were determined, the median TMB value was 5.4 Muts/Mb (range 0-28.4 Muts/Mb), and the 75% TMB line was 7.7 Muts/Mb. The most common mutant genes are TP53, TERT, CTNNB1, AXIN1, RB1, TSC2, CCND1, ARID1A and FGF19. SNV is the most common type of mutation, G:C>T:A and guanine transformation are the most common SNV.
        Compared with wild-type patients, the proportion of Edmondson grade III-IV and microvascular infiltration in patients with TP53 mutation was significantly higher (p<0.05). In patients with TERT mutations, the proportion of tumors invading the liver capsule was significantly higher (p<0.05). Among CTNNB1 mutation patients, the proportion of Edmondson grade I-II, alpha-fetoprotein (AFP) <25 μmg/L and no history of hepatitis B was significantly increased (p<0.05). CTNNB1 mutation is associated with high TMB (p<0.05).
        Correlation analysis showed that TP53 mutation was independently associated with microvascular invasion (p=0.002, OR=3.096) and Edmondson III-IV grade (p=0.008, OR=2.613). TERT mutation was independently associated with liver envelope tumor invasion (p=0.001, OR=3.030). CTNNB1 mutation was independently associated with AFP (<25 μmg/L) (p=0.009, OR=3.414).
        In summary, the most common mutated genes in Chinese HCC patients are TP53, TERT and CTNNB1. These genes may lead to the occurrence and development of HCC by regulating the TP53 pathway, Wnt signaling pathway and telomere repair pathway. Moreover, patients with different gene mutations often have different clinical characteristics.


Original source:

Wang Shuo，Shi Huasheng，Liu Tao et al. Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients. Hepatobiliary Surg Nutr， 2021， 10： 172-179