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.
摘要：
端粒酶逆转录酶（TERT）和β-catenin（CTNNB1）突变可能发生在肝细胞癌（HCC）通路信号之后。我们对408例经病理手术诊断为HCC的患者进行了层次聚类分析研究。通过测序鉴定TERT启动子和CTNNB1外显子3突变。总体临床前特征，累积切点值，并在单/多维缩放模型中分析与这些体细胞突变相关的因素。HBV（+）HCV（-）HCC男性患者年龄大于62.74岁，TERT启动子突变以及AFP>489.78ng/ml将获得更高的HCC等级风险，从27％到200％p<0.05（RR从1.27[1.09-1.47]到3.06[2.04-4.61]）。该突变是2级风险的良好指标（HR=0.37[2.72-0.16]，β=-1.00，p=0.019）。TERT启动子和CTNNB1外显子3突变独立影响3级和HBV（-）HCV（-）男性HCC患者的肿瘤大小和肿瘤部位状态，危险发生率，分别,为0.28[0.09-0.89]，0.023[0.0023-0.23]和0.06[0.012-0.32](β<0和p<0.01)。这两种突变对肿瘤部位的状态产生了相反的影响，尤其是在2级无B的男性HCC患者中，丙型肝炎病毒（RRCTNNB1外显子3突变-TERT启动子野生型=1.12[1.04-1.20]，p<0.05)。因此,TERT启动子和CTNNB1外显子3的突变可能与其他因素同步或独立影响肝癌的发生,并且是AFP水平非常高或肿瘤中中度和低分化的男性患者HCC预后的重要指标.我们的结果作为进一步研究的基础，以了解不同因素对HCC结果的影响。特别是在监测和评估患者感染HBV和携带突变的癌症风险。
