Mutation profile and its correlation with clinicopathology in Chinese hepatocellular carcinoma patients.

BACKGROUND

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer worldwide. Although many studies have focused on oncogene characteristics, the genomic landscape of Chinese HCC patients has not been fully clarified.

METHODS

A total of 165 HCC patients, including 146 males and 19 females, were enrolled. The median age was 55 years (range, 27-78 years). Corresponding clinical and pathological information was collected for further analysis. A total of 168 tumor tissues from these patients were selected for next-generation sequencing (NGS)-based 450 panel gene sequencing. Genomic alterations including single nucleotide variations (SNV), short and long insertions and deletions (InDels), copy number variations, and gene rearrangements were analyzed. Tumor mutational burden (TMB) was measured by an algorithm developed in-house. The top quartile of HCC was classified as TMB high.

RESULTS

A total of 1,004 genomic alterations were detected from 258 genes in 168 HCC tissues. TMB values were identified in 160 HCC specimens, with a median TMB of 5.4 Muts/Mb (range, 0-28.4 Muts/Mb) and a 75% TMB of 7.7 Muts/Mb. The most commonly mutated genes were , and . SNV was the most common mutation type and C:G>T:A and guanine transformation were the most common SNVs. Compared to wild-type patients, the proportion of Edmondson grade III-IV and microvascular invasion was significantly higher in mutated patients (P<0.05). The proportion of tumors invading the hepatic capsule was significantly higher in mutated patients (P<0.05). The proportion of Edmondson grade I-II, alpha fetoprotein (AFP) <25 µmg/L, and those without a history of hepatitis B was significantly higher in mutated patients (P<0.05). mutations were associated with TMB high in HCC patients (P<0.05). Based on correlation analysis, the mutation of was independently correlated with microvascular invasion (P=0.002, OR =3.096) and Edmondson grade III-IV (P=0.008, OR =2.613). The mutation of was independently correlated with tumor invasion of the liver capsule (P=0.001, OR =3.030), and the mutation of was independently correlated with AFP (<25 µmg/L) (P=0.009, OR =3.414).

CONCLUSIONS

The most frequently mutated genes of HCC patients in China were , , and , which mainly lead to the occurrence and development of HCC by regulating the P53 pathway, Wnt pathway, and telomere repair pathway. There were more patients with microvascular invasion and Edmondson III-IV grade in mutated patients and more patients with hepatic capsule invasion in mutated patients, while in mutated patients, there were more patients with Edmondson I-II grade, AFP <25 µmg/L, and a non-hepatitis B background. Also, the TMB values were significantly higher in mutated patients than in wild type patients.