Kim Kyeezu, Zheng Yinan, Joyce Brian T, Nannini Drew R, Wang Jun, Qu Yishu, Hawkins Claudia A, Okeke Edith, Lesi Olufunmilayo A, Roberts Lewis R, Gursel Demirkan B, Abdulkareem Fatimah B, Akanmu Alani S, Duguru Mary J, Davwar Pantong, Nyam David Paul, Adisa Rahmat A, Imade Godwin, Wei Jian-Jun, Kocherginsky Masha, Kim Kwang-Youn, Adeyemo Wasiu L, Odeghe Emuobor, Wehbe Firas H, Achenbach Chad, Sagay Atiene, Ogunsola Folasade, Murphy Robert L, Hou Lifang
Sungkyunkwan University School of Medicine, 2066 Seobu-ro, Jangan-gu, Suwon-si, Gyeonggi-do, 16419, South Korea.
Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Hepatol Int. 2025 Jun;19(3):596-606. doi: 10.1007/s12072-024-10768-1. Epub 2024 Dec 20.
People living with the human immunodeficiency virus (HIV) are at a greater risk of developing hepatocellular carcinoma (HCC), potentially due to the stimulation of inflammation by HIV infection. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (cfDNA), may serve as promising minimally invasive biomarkers that can inform diagnosis of HCC.
Using data from 249 individuals with HIV (114 individuals with normal liver conditions, 69 with fibrosis, 30 with cirrhosis, and 36 with HCC), we constructed a cfDNA methylation-based inflammation score (inflammation-DNAm score) based on 54 CpGs previously associated with circulating C-reactive protein concentrations. Associations of DNAm scores with HCC were assessed using multivariable logistic regression models. Receiver operating characteristic analysis was conducted to assess the performance of discriminating HCC between the inflammation-DNAm score and alpha-fetoprotein (AFP), one of the current screening biomarkers.
A higher inflammation-DNAm score was associated with a 29% increase in the odds of HCC (OR = 1.29, 95% CI = 1.01-1.65). The association remained consistent in the models adjusted for cellular origin proportions. The DNAm score exhibited superior performance in discriminating HCC from controls (AUC = 0.94, 95% CI = 0.90-0.98), compared to AFP (AUC = 0.68, 95% CI = 0.51-0.85).
Our findings suggest that cfDNA methylation-based biomarkers may aid in the detection of HCC in people living with HIV, a population at high-risk of developing HCC.
感染人类免疫缺陷病毒（HIV）的人群患肝细胞癌（HCC）的风险更高，这可能是由于HIV感染引发的炎症刺激所致。在液体活检中获得的与炎症相关的DNA甲基化特征，如循环游离DNA（cfDNA），可能成为有前景的微创生物标志物，有助于HCC的诊断。
我们利用来自249名HIV感染者的数据（114名肝功能正常者、69名纤维化患者、30名肝硬化患者和36名HCC患者），基于先前与循环C反应蛋白浓度相关的54个CpG构建了基于cfDNA甲基化的炎症评分（炎症-DNAm评分）。使用多变量逻辑回归模型评估DNAm评分与HCC的关联。进行了受试者操作特征分析，以评估炎症-DNAm评分与当前筛查生物标志物之一甲胎蛋白（AFP）鉴别HCC的性能。
较高的炎症-DNAm评分与HCC发生几率增加29%相关（OR = 1.29，95%CI = 1.01 - 1.65）。在根据细胞来源比例调整的模型中，该关联保持一致。与AFP（AUC = 0.68，95%CI = 0.51 - 0.85）相比，DNAm评分在鉴别HCC与对照方面表现更优（AUC = 0.94，95%CI = 0.90 - 0.98）。
我们的研究结果表明，基于cfDNA甲基化的生物标志物可能有助于在感染HIV且有HCC高发病风险的人群中检测HCC。
