Song Yinghui, Xu Ming, Li Yufeng, Zhang Xinling, Xu Wei
Central Laboratory, Hunan Provincial People's Hospital (the First Affiliated Hospital of Hunan Normal University), Changsha, 410000, China.
The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, China.
Sci Rep. 2025 Jul 2;15(1):23303. doi: 10.1038/s41598-025-06507-7.
Hepatocellular carcinoma (HCC) ranked as the sixth most common malignancy and the third leading cause of cancer-related mortality with approximately 830, 000 deaths worldwide annually. Genetic instability of short tandem repeats (STRs), which manifested as loss of heterozygosity (LOH) or microsatellite instability (MSI) in the cancerous cells, is a genetic feature of many types of human cancers. The status of STR instablility and its clinical significance in HCC, however, remains to be comprehensively elucidated. In this study, a total of 101 matched DNA samples from HCC individuals were analyzed with 20 "classical STR markers widely used in forensic genetics, our findings demonstrated that 79.21% (80/101) of HCC cases exhibited genetic alterations in at least 1 STR locus, with 16.73% of STR loci altered across all samples. Moreover, our findings also revealed a significant association between an accumulation of STR alterations and the presence of positive hepatitis B surface antigen (HBsAg), as well as moderate-poor/poor differentiation of HCC. Furthermore, LOH at the FGA was found to be significantly correlated with moderate-poor/poor differentiation of HCC (p = 0.002), and LOH at the D16S539 was found to be significantly associated with elevated serum levels of AFP (p = 0.042) as well as larger tumor sizes (p = 0.040). Overall, this study contributes valuable insights into the genetic instability of STRs in HCC and might also enhance insights into the intricate mechanisms underlying hepatocarcinogenesis.
肝细胞癌(HCC)是全球第六大常见恶性肿瘤,也是癌症相关死亡的第三大主要原因,全球每年约有83万人死亡。短串联重复序列(STR)的基因不稳定性表现为癌细胞中的杂合性缺失(LOH)或微卫星不稳定性(MSI),是多种人类癌症的遗传特征。然而,HCC中STR不稳定性的状态及其临床意义仍有待全面阐明。在本研究中,我们使用法医遗传学中广泛使用的20个“经典STR标记”对101例HCC患者的匹配DNA样本进行了分析,结果表明,79.21%(80/101)的HCC病例在至少1个STR位点存在基因改变,所有样本中16.73%的STR位点发生改变。此外,我们的研究结果还显示,STR改变的积累与乙肝表面抗原(HBsAg)阳性以及HCC的中低分化/低分化之间存在显著关联。此外,发现FGA位点的LOH与HCC的中低分化/低分化显著相关(p = 0.002),D16S539位点的LOH与血清甲胎蛋白(AFP)水平升高(p = 0.042)以及肿瘤较大(p = 0.040)显著相关。总体而言,本研究为HCC中STR的基因不稳定性提供了有价值的见解,也可能有助于深入了解肝癌发生的复杂机制。