Scholarlink

<p>Hepatocellular carcinoma (HCC) is characterized by profound metabolic reprogramming and immune heterogeneity, yet transcriptomic markers that reflect tumor-specific metabolic states remain limited. UDP-glucuronosyltransferases (UGTs) are key hepatic enzymes involved in detoxification and glucuronidation, but their systematic transcriptional landscape and clinical relevance in HCC have not been comprehensively explored. Here, we performed a comprehensive multi-cohort transcriptomic analysis of all 19 functional UGT family genes across TCGA-LIHC, GepLiver, GEPIA3, HCCDB, and an independent institutional cohort. Across datasets, most UGT genes exhibited global transcriptional downregulation with minimal genomic alterations, indicating that dysregulated expression rather than structural variation predominates in HCC. Among them, <i>UGT2B11</i> uniquely demonstrated consistent upregulation, a markedly higher proportion of high-expression cases, and reproducible diagnostic performance across multiple cohorts. In the GepLiver and institutional cohorts, <i>UGT2B11</i> expression was significantly elevated in HCC compared with normal and adjacent liver tissues, yielding area-under-the-curve values ranging from 0.79 to 0.84. Pathway enrichment analyses of genes correlated with <i>UGT2B11</i> revealed strong enrichment of glucuronidation-related pathways, consistent with canonical UGT function, while also identifying mTORC1 signaling as a recurrent transcriptional feature modestly associated with <i>UGT2B11</i> expression. Single-cell RNA-sequencing analyses demonstrated that <i>UGT2B11</i> expression is largely confined to malignant hepatocyte populations, supporting its tumor-specific transcriptional activation. In parallel, immune infiltration analyses revealed significant positive associations between <i>UGT2B11</i> expression and multiple immune cell signatures, most prominently Tregs, further supported by correlations with established Treg-associated genes. Collectively, this study delineates the transcriptomic landscape of the UGT family in HCC and identifies <i>UGT2B11</i> as a tumor-associated metabolic transcript with reproducible diagnostic potential, while showing modest associations with mTORC1-related transcriptional programs and immune features.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Systematic transcriptomic analysis of UDP-glucuronosyltransferases reveals UGT2B11 as a diagnostic and metabolic marker in hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月22日

查看全文
  • Hyun Sun Jung,
  • Geum Ok Baek,
  • Moon Gyeong Yoon,
  • Se Ha Jang,
  • Jae Youn Cheong,
  • Soon Sun Kim,
  • Jung Woo Eun

摘要

Hepatocellular carcinoma (HCC) is characterized by profound metabolic reprogramming and immune heterogeneity, yet transcriptomic markers that reflect tumor-specific metabolic states remain limited. UDP-glucuronosyltransferases (UGTs) are key hepatic enzymes involved in detoxification and glucuronidation, but their systematic transcriptional landscape and clinical relevance in HCC have not been comprehensively explored. Here, we performed a comprehensive multi-cohort transcriptomic analysis of all 19 functional UGT family genes across TCGA-LIHC, GepLiver, GEPIA3, HCCDB, and an independent institutional cohort. Across datasets, most UGT genes exhibited global transcriptional downregulation with minimal genomic alterations, indicating that dysregulated expression rather than structural variation predominates in HCC. Among them, UGT2B11 uniquely demonstrated consistent upregulation, a markedly higher proportion of high-expression cases, and reproducible diagnostic performance across multiple cohorts. In the GepLiver and institutional cohorts, UGT2B11 expression was significantly elevated in HCC compared with normal and adjacent liver tissues, yielding area-under-the-curve values ranging from 0.79 to 0.84. Pathway enrichment analyses of genes correlated with UGT2B11 revealed strong enrichment of glucuronidation-related pathways, consistent with canonical UGT function, while also identifying mTORC1 signaling as a recurrent transcriptional feature modestly associated with UGT2B11 expression. Single-cell RNA-sequencing analyses demonstrated that UGT2B11 expression is largely confined to malignant hepatocyte populations, supporting its tumor-specific transcriptional activation. In parallel, immune infiltration analyses revealed significant positive associations between UGT2B11 expression and multiple immune cell signatures, most prominently Tregs, further supported by correlations with established Treg-associated genes. Collectively, this study delineates the transcriptomic landscape of the UGT family in HCC and identifies UGT2B11 as a tumor-associated metabolic transcript with reproducible diagnostic potential, while showing modest associations with mTORC1-related transcriptional programs and immune features.