Supplementary Material for: Favorable impact of serum TERT C228T for prognosis after surgical resection for liver cancer

Introduction: Personalized medicine and molecular therapies with the diagnosis of somatic genetic alterations are expected to be developed for liver cancer. Nevertheless, it is unknown whether a mutation in the telomere reverse transcriptase promoter (TERT C228T) in serum cfDNA might be useful for making prognostic predictions after surgical resection for primary liver cancer. Methods: This cohort study retrospectively investigated 111 patients who had undergone surgical resection of liver cancer for the first time. We investigated the differences between clinicopathological features and prognosis according to classification of three tumor markers, including AFP, PIVKAII, and TERT C228T. Results: Multivariate analysis identified etiology (fatty liver disease versus HBV Odds ratio [OR] 6.853) and fibrosis stage (2–4, OR 0.137) as determinants of TERT C228T-positive liver cancer with normal levels of AFP and PIVKAII (TERT single positive liver cancer). TERT single positive (Yes, OR 0.301), fibrosis (FIB)-4 index (≥ 3.25, OR 2.038), Child–Pugh classification (B, OR 4.975), and number of tumors (≥ 2, OR 4.098) were identified as determinants of the recurrence of liver cancer. TERT single positive (Yes, OR 3.311), FIB-4 index (≥ 3.25, OR 0.433), and number of tumors (≥ 2, OR 0.262) were identified as determinants of disease-free survival. Conclusions: Our results highlight the impact of classification of prognostic tumor markers. TERT single positive is one predictor of favorable prognosis after surgical resection for liver cancer.

引言：针对肝癌的个体化诊疗与基于体细胞遗传变异检测的分子治疗方案已成为研究热点。然而，血清细胞游离DNA（cell-free DNA, cfDNA）中端粒逆转录酶启动子（telomere reverse transcriptase promoter, TERT C228T）突变是否可用于原发性肝癌术后预后预测，目前尚无定论。
方法：本队列研究回顾性分析了111例首次接受肝癌手术切除的患者，根据甲胎蛋白（Alpha-fetoprotein, AFP）、异常凝血酶原（protein induced by vitamin K absence or antagonist Ⅱ, PIVKA-II）及TERT C228T三种肿瘤标志物的分类情况，分析了患者临床病理特征与预后的差异。
结果：多因素分析显示，病因（脂肪性肝病 vs 乙型肝炎病毒感染，比值比[Odds Ratio, OR] 6.853）与纤维化分期（2~4期，OR 0.137）是AFP与PIVKA-II水平正常的TERT C228T阳性肝癌（即TERT单阳性肝癌）的独立影响因素。TERT单阳性（是，OR 0.301）、肝纤维化4指数（FIB-4 index, FIB-4）≥3.25（OR 2.038）、Child-Pugh分级为B级（OR 4.975）以及肿瘤数目≥2个（OR 4.098）为肝癌复发的独立影响因素。TERT单阳性（是，OR 3.311）、FIB-4指数≥3.25（OR 0.433）以及肿瘤数目≥2个（OR 0.262）为无病生存期的独立影响因素。
结论：本研究结果凸显了预后肿瘤标志物分类的临床价值，TERT单阳性是肝癌手术切除后良好预后的预测因素之一。