Akuta Norio, Kawamura Yusuke, Suzuki Fumitaka, Kobayashi Mariko, Arase Yasuji, Saitoh Satoshi, Muraishi Nozomu, Fujiyama Shunichiro, Sezaki Hitomi, Hosaka Tetsuya, Kobayashi Masahiro, Suzuki Yoshiyuki, Ikeda Kenji, Kumada Hiromitsu
Department of Hepatology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo, 105-8470, Japan.
Liver Research Laboratory, Toranomon Hospital, Tokyo, Japan.
Hepatol Int. 2022 Apr;16(2):412-422. doi: 10.1007/s12072-022-10313-y. Epub 2022 Mar 20.
Molecular therapies and precision medicine are expected to be developed for liver cancer based on the diagnosis of DNA somatic alterations. However, it remains unclear whether TERT promoter mutation (TERT C228T) in serum cfDNA is useful for the diagnosis of liver cancer with non-viral fatty liver disease (FLD).
This retrospective cohort study examined 258 Japanese patients who had a confirmed diagnosis of primary liver cancer. We investigated the factors associated with TERT C228T and abnormal levels of liver cancer-specific tumor markers (AFP and PIVKAII) in serum samples.
Multivariate analysis identified the etiology of FLD, vascular invasion, and non-cirrhosis as determinants of TERT C228T-positive liver cancer. Rates of positive TERT C228T in FLD were significantly higher than those of HBV and HCV. Conversely, rates of abnormal AFP in FLD were significantly lower than those of HBV and HCV. Viral suppression of HBV/HCV and alcohol intake did not affect TERT C228T, but AFP was significantly reduced by viral suppression. The rates of positive TERT C228T were significantly lower in HCV patients with viral clearance than those of FLD patients.
Our results highlight the importance of serum TERT C228T for the detection of non-viral FLD-related liver cancer. TERT C228T is a tumor marker that might not be influenced by inflammation.
基于DNA体细胞改变的诊断，有望为肝癌开发分子疗法和精准医学。然而，血清游离DNA中的端粒酶逆转录酶（TERT）启动子突变（TERT C228T）对非病毒性脂肪性肝病（FLD）相关肝癌的诊断是否有用仍不清楚。
这项回顾性队列研究检查了258例确诊为原发性肝癌的日本患者。我们调查了血清样本中与TERT C228T以及肝癌特异性肿瘤标志物（甲胎蛋白和异常凝血酶原II）水平异常相关的因素。
多变量分析确定FLD的病因、血管侵犯和非肝硬化是非病毒性脂肪性肝病相关肝癌的决定因素。FLD患者中TERT C228T阳性率显著高于乙肝和丙肝患者。相反，FLD患者中甲胎蛋白异常率显著低于乙肝和丙肝患者。乙肝/丙肝病毒抑制和酒精摄入不影响TERT C228T，但病毒抑制可显著降低甲胎蛋白水平。丙肝病毒清除患者中TERT C228T阳性率显著低于FLD患者。
我们的结果突出了血清TERT C228T对检测非病毒性脂肪性肝病相关肝癌的重要性。TERT C228T是一种可能不受炎症影响的肿瘤标志物。
