{"title":"持续病毒学应答后肝细胞癌的遗传改变与代谢性疾病的分子特征有关。","authors":"Fukiko Kawai-Kitahata, Yasuhiro Asahina, Sei Kakinuma, Kento Inada, Tomohiro Mochida, Keiya Watakabe, Tsubasa Nobusawa, Taro Shimizu, Jun Tsuchiya, Masato Miyoshi, Shun Kaneko, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Yuko Kinowaki, Daisuke Ban, Shinji Tanaka, Tatsuhiko Anzai, Shinichi Takano, Shinya Maekawa, Nobuyuki Enomoto, Ryuichi Okamoto","doi":"10.1111/hepr.14214","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong>The mechanism of hepatocarcinogenesis after sustained virological response (SVR) in hepatitis C virus (HCV) patients is unclear. We compared gene profiles of hepatocellular carcinoma (HCC) between HCV-SVR, steatotic liver disease (SLD), and HCV-non-SVR patients.</p><p><strong>Methods: </strong>This study analyzed 126 resected HCCs from patients with HCV and SLD, classifying them as HCV-SVR (n = 22), HCV-non-SVR (n = 56), and SLD (n = 48). Deep sequencing of 2910 hotspots in 55 cancer-related genes was conducted to examine mutations and copy number variations in both cancerous and background liver tissues.</p><p><strong>Results: </strong>The HCV-SVR group comprised more patients who consumed alcohol (45.5% vs. 15.7%, p = 0.008), were obese (54.5% vs. 17.9%, p = 0.002), and had dyslipidemia (18.2% vs. 3.6%, p = 0.029) and hyperuricemia (18.2% vs. 3.6%, p = 0.029) than the HCV-non-SVR group. Mutational profiling of the HCV-SVR HCC showed significantly lower alteration rates of AXIN1 (13.6% vs. 42.9%, p = 0.016), ARID2 (9.1% vs. 39.3%, p = 0.013), and TP53 (9.1% vs. 32.1%, p = 0.030) than HCV-non-SVR patients. Compared with HCV-non-SVR-HCC, SLD-HCCs showed significantly lower rates of TERT promoter mutations (62.5% vs. 85.7%, p = 0.004), ARID2 alterations (12.5% vs. 39.3%, p = 0.003), and AXIN1 alterations (12.5% vs. 42.9%, p = 0.002). HCV-SVR/MASH/MASLD/ALD-HCC had significantly lower alteration rates of the Wnt/β-catenin (41.4% vs. 60.7%, p = 0.048) and chromatin remodeling pathways (27.1% vs. 48.2%, p = 0.026) than HCV-non-SVR-HCC.</p><p><strong>Conclusions: </strong>HCV-SVR HCC is linked to alcohol use and metabolic diseases, showing a mutational profile similar to SLD-HCC.</p>","PeriodicalId":12987,"journal":{"name":"Hepatology Research","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genetic alterations in hepatocellular carcinoma after sustained virological response in relation to the molecular characterization of metabolic diseases.\",\"authors\":\"Fukiko Kawai-Kitahata, Yasuhiro Asahina, Sei Kakinuma, Kento Inada, Tomohiro Mochida, Keiya Watakabe, Tsubasa Nobusawa, Taro Shimizu, Jun Tsuchiya, Masato Miyoshi, Shun Kaneko, Miyako Murakawa, Sayuri Nitta, Mina Nakagawa, Yuko Kinowaki, Daisuke Ban, Shinji Tanaka, Tatsuhiko Anzai, Shinichi Takano, Shinya Maekawa, Nobuyuki Enomoto, Ryuichi Okamoto\",\"doi\":\"10.1111/hepr.14214\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong>The mechanism of hepatocarcinogenesis after sustained virological response (SVR) in hepatitis C virus (HCV) patients is unclear. We compared gene profiles of hepatocellular carcinoma (HCC) between HCV-SVR, steatotic liver disease (SLD), and HCV-non-SVR patients.</p><p><strong>Methods: </strong>This study analyzed 126 resected HCCs from patients with HCV and SLD, classifying them as HCV-SVR (n = 22), HCV-non-SVR (n = 56), and SLD (n = 48). Deep sequencing of 2910 hotspots in 55 cancer-related genes was conducted to examine mutations and copy number variations in both cancerous and background liver tissues.</p><p><strong>Results: </strong>The HCV-SVR group comprised more patients who consumed alcohol (45.5% vs. 15.7%, p = 0.008), were obese (54.5% vs. 17.9%, p = 0.002), and had dyslipidemia (18.2% vs. 3.6%, p = 0.029) and hyperuricemia (18.2% vs. 3.6%, p = 0.029) than the HCV-non-SVR group. Mutational profiling of the HCV-SVR HCC showed significantly lower alteration rates of AXIN1 (13.6% vs. 42.9%, p = 0.016), ARID2 (9.1% vs. 39.3%, p = 0.013), and TP53 (9.1% vs. 32.1%, p = 0.030) than HCV-non-SVR patients. Compared with HCV-non-SVR-HCC, SLD-HCCs showed significantly lower rates of TERT promoter mutations (62.5% vs. 85.7%, p = 0.004), ARID2 alterations (12.5% vs. 39.3%, p = 0.003), and AXIN1 alterations (12.5% vs. 42.9%, p = 0.002). HCV-SVR/MASH/MASLD/ALD-HCC had significantly lower alteration rates of the Wnt/β-catenin (41.4% vs. 60.7%, p = 0.048) and chromatin remodeling pathways (27.1% vs. 48.2%, p = 0.026) than HCV-non-SVR-HCC.</p><p><strong>Conclusions: </strong>HCV-SVR HCC is linked to alcohol use and metabolic diseases, showing a mutational profile similar to SLD-HCC.</p>\",\"PeriodicalId\":12987,\"journal\":{\"name\":\"Hepatology Research\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Hepatology Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/hepr.14214\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/hepr.14214","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
目的：丙型肝炎病毒（HCV）患者持续病毒学反应（SVR）后肝癌发生机制尚不清楚。我们比较了HCV-SVR、脂肪变性肝病（SLD）和hcv -非svr患者的肝细胞癌（HCC）基因谱。方法：本研究分析了126例HCV合并SLD患者切除的hcc，将其分为HCV- svr （n = 22）、HCV-非svr （n = 56）和SLD （n = 48）。对55个癌症相关基因的2910个热点进行深度测序，以检测癌性和背景肝组织中的突变和拷贝数变化。结果：与hcv -非svr组相比，HCV-SVR组有更多的患者饮酒（45.5%比15.7%,p = 0.008）、肥胖（54.5%比17.9%,p = 0.002）、血脂异常（18.2%比3.6%,p = 0.029）和高尿酸血症（18.2%比3.6%,p = 0.029）。HCV-SVR HCC的突变谱显示，与hcv -非svr患者相比，AXIN1（13.6%比42.9%,p = 0.016）、ARID2（9.1%比39.3%,p = 0.013）和TP53（9.1%比32.1%,p = 0.030）的变化率显著降低。与HCV-non-SVR-HCC相比，sld - hcc的TERT启动子突变率（62.5% vs. 85.7%, p = 0.004）、ARID2改变率（12.5% vs. 39.3%, p = 0.003）和AXIN1改变率（12.5% vs. 42.9%, p = 0.002）均显著降低。HCV-SVR/MASH/MASLD/ALD-HCC的Wnt/β-catenin改变率（41.4%比60.7%,p = 0.048）和染色质重塑途径改变率（27.1%比48.2%,p = 0.026）显著低于HCV-non-SVR-HCC。结论：HCV-SVR HCC与酒精使用和代谢性疾病有关，显示出与SLD-HCC相似的突变谱。
Genetic alterations in hepatocellular carcinoma after sustained virological response in relation to the molecular characterization of metabolic diseases.
Aim: The mechanism of hepatocarcinogenesis after sustained virological response (SVR) in hepatitis C virus (HCV) patients is unclear. We compared gene profiles of hepatocellular carcinoma (HCC) between HCV-SVR, steatotic liver disease (SLD), and HCV-non-SVR patients.
Methods: This study analyzed 126 resected HCCs from patients with HCV and SLD, classifying them as HCV-SVR (n = 22), HCV-non-SVR (n = 56), and SLD (n = 48). Deep sequencing of 2910 hotspots in 55 cancer-related genes was conducted to examine mutations and copy number variations in both cancerous and background liver tissues.
Results: The HCV-SVR group comprised more patients who consumed alcohol (45.5% vs. 15.7%, p = 0.008), were obese (54.5% vs. 17.9%, p = 0.002), and had dyslipidemia (18.2% vs. 3.6%, p = 0.029) and hyperuricemia (18.2% vs. 3.6%, p = 0.029) than the HCV-non-SVR group. Mutational profiling of the HCV-SVR HCC showed significantly lower alteration rates of AXIN1 (13.6% vs. 42.9%, p = 0.016), ARID2 (9.1% vs. 39.3%, p = 0.013), and TP53 (9.1% vs. 32.1%, p = 0.030) than HCV-non-SVR patients. Compared with HCV-non-SVR-HCC, SLD-HCCs showed significantly lower rates of TERT promoter mutations (62.5% vs. 85.7%, p = 0.004), ARID2 alterations (12.5% vs. 39.3%, p = 0.003), and AXIN1 alterations (12.5% vs. 42.9%, p = 0.002). HCV-SVR/MASH/MASLD/ALD-HCC had significantly lower alteration rates of the Wnt/β-catenin (41.4% vs. 60.7%, p = 0.048) and chromatin remodeling pathways (27.1% vs. 48.2%, p = 0.026) than HCV-non-SVR-HCC.
Conclusions: HCV-SVR HCC is linked to alcohol use and metabolic diseases, showing a mutational profile similar to SLD-HCC.
期刊介绍：
Hepatology Research (formerly International Hepatology Communications) is the official journal of the Japan Society of Hepatology, and publishes original articles, reviews and short comunications dealing with hepatology. Reviews or mini-reviews are especially welcomed from those areas within hepatology undergoing rapid changes. Short communications should contain concise definitive information.
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