A systematic analysis with the hierarchical cluster analysis strategy on the complex interaction of TERT and CTNNB1 somatic mutations in Vietnamese hepatocellular carcinoma patients

Abstract

Telomerase reverse transcriptase (TERT) and β-catenin (CTNNB1) mutations may occur following the hepatocellular carcinoma (HCC) pathway signal. We conducted a Hierarchical cluster analysis study on 408 patients diagnosed with HCC by pathological surgery, identifying TERT promoter and CTNNB1 exon 3 mutations by sequencing. The overall preclinical characteristics, cumulative cut-point values, and the factors associated with these somatic mutations were analyzed in uni/multidimensional scaling model. HBV(+) HCV(−) HCC male patients who were older than 62.74 years old and have TERT promoter mutation as well as AFP > 489.78 ng/ml got a higher risk of HCC grade more than two from 27 % to 200 % with p < 0.05 (RR are from 1.27 [1.09–1.47] to 3.06 [2.04–4.61]). This mutation was a good indicator of grade 2 risk (HR = 0.37 [2.72–0.16], β = −1.00, p = 0.019). TERT promoter and CTNNB1 exon 3 mutations independently influenced tumor size and tumor site status in grade 3 and HBV(−) HCV (−) male HCC patients, where the hazard rates, respectively, were 0.28 [0.09–0.89], 0.023 [0.0023–0.23] and 0.06 [0.012–0.32] (β < 0 and p < 0.01). These two mutations inversely impacted each other the tumor sites status, especially in male HCC patients with grade 2 without B, C hepatitis virus (RRCTNNB1 exon 3 mutate - TERT promoter wildtype = 1.12 [1.04–1.20], p < 0.05). Consequently, the mutations in TERT promoter and CTNNB1 exon 3 may synchronize with other factors or independently impact the hepatocarcinogenesis and are important indicators for HCC prognostic in male patients with very high AFP levels or with moderately as well as poorly differentiated in tumor. Our results serve as the basis for further studies to understand the impact of different factors on the outcome of HCC, especially in monitoring and assessing the cancer risk of patients infect HBV and carry mutations.