Kim Hyung Seok, Jang Se Ha, Baek Geum Ok, Yoon Moon Gyeong, Shim Jaewon, Han Ji Eun, Kim Soon Sun, Cheong Jae Youn, Eun Jung Woo
Department of Biochemistry, Kosin University College of Medicine, Seo-gu, Busan 49267, Republic of Korea.
Department of Gastroenterology, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea.
Curr Issues Mol Biol. 2025 Jul 18;47(7):563. doi: 10.3390/cimb47070563.
Hepatocellular carcinoma (HCC) critically lacks reliable biomarkers for early detection. By mining the TCGA_LIHC and two GEO cohorts, we identified the liver-specific long non-coding RNA as the most consistently down-regulated transcript in tumors. This finding was validated in 97 paired tissues, with expression lost in 95% of cases (*** < 0.0001). It demonstrated excellent diagnostic performance in discriminating tumor from non-tumor tissue (AUC = 0.95), which was maintained in early-stage (I/II) disease. Low expression correlated with shorter overall and disease-free survival and was inversely associated with serum α-fetoprotein (AFP) levels, highlighting its complementary clinical value. Mechanistic investigation revealed a potential competing endogenous RNA (ceRNA) axis. The microRNA miR-190b-5p was highly expressed in tumors and predicted to bind , while its target, , was significantly suppressed. Survival analysis confirmed that concurrent high expression of and conferred superior outcomes. These findings establish as a liver-specific, ceRNA-mediated tumor suppressor with robust diagnostic and prognostic potential. It represents a promising adjunct to existing HCC surveillance strategies, such as ultrasound and AFP measurement, for high-risk populations.
肝细胞癌（HCC）严重缺乏用于早期检测的可靠生物标志物。通过挖掘TCGA_LIHC和两个GEO队列，我们确定肝脏特异性长链非编码RNA是肿瘤中最持续下调的转录本。这一发现在97对配对组织中得到验证，95%的病例中该基因表达缺失（***P < 0.0001）。它在区分肿瘤组织与非肿瘤组织方面表现出优异的诊断性能（AUC = 0.95），在早期（I/II期）疾病中也保持这一性能。该基因低表达与较短的总生存期和无病生存期相关，且与血清甲胎蛋白（AFP）水平呈负相关，突出了其互补的临床价值。机制研究揭示了一个潜在的竞争性内源性RNA（ceRNA）轴。微小RNA miR-190b-5p在肿瘤中高表达且预测可与该基因结合，而其靶标基因则被显著抑制。生存分析证实该基因与miR-190b-5p同时高表达可带来更好的预后。这些发现确立了该基因作为一种肝脏特异性、ceRNA介导的肿瘤抑制因子，具有强大的诊断和预后潜力。它代表了一种有前景的辅助手段，可用于现有针对高危人群的HCC监测策略，如超声检查和AFP测量。
