HCV相关肝硬化转变为肝癌期间,单核细胞亚群分布异常并且血浆hsa-miR-21-5p和hsa-miR-155-5p被失调。
Monocytes subsets altered distribution and dysregulated plasma hsa-miR-21-5p and hsa-miR-155-5p in HCV-linked liver cirrhosis progression to hepatocellular carcinoma.
发表日期:2023 Aug 28
作者:
Reham Hammad, Mona A Eldosoky, Asmaa A Elmadbouly, Reda Badr Aglan, Sherihan G AbdelHamid, Samy Zaky, Elham Ali, Fatma El-Zahraa Abd El Hakam, Alshaimaa M Mosaad, Neamat A Abdelmageed, Fatma M Kotb, Hend G Kotb, Ahmed A Hady, Omaima I Abo-Elkheir, Sandy Kujumdshiev, Ulrich Sack, Claude Lambert, Nadia M Hamdy
来源:
CLINICAL PHARMACOLOGY & THERAPEUTICS
摘要:
作者的目的是研究在肝硬化(LC)和随后的肝细胞癌(HCC)中,单核细胞亚群分布的改变与血浆Homo sapiens(has)-miR-21-5p和hsa-miR-155-5p的表达水平的关联。这是非蛋白编码(nc)RNA基于免疫紊乱而进行的精准医学的一步,表现为单核细胞分布的改变,基于LC和HCC的基础之上。本研究纳入了79例被诊断为慢性丙型肝炎病毒(CHCV)感染并患有LC的患者。将患者分为没有HCC的LC组(n = 40),LC与HCC组(n = 39)和15名明显健康的对照组。流式细胞术评估了单核细胞亚群的频率。实时定量PCR用于测量血浆hsa-miR-21-5p和hsa-miR-155-5p的表达。Hsa-miR-21-5p与中间型单核细胞呈正相关(r = 0.30,p = 0.007),而hsa-miR-155-5p与非经典型单核细胞呈负相关(r = -0.316,p = 0.005)。ROC曲线分析显示,组合中间型单核细胞频率和hsa-miR-21的灵敏度= 79.5%,特异度= 75%,AUC = 0.84。相比之下,AFP的灵敏度= 69%,特异度= 100%,AUC = 0.85。经过共同调节因素调整后,Logistic回归分析证明中间型单核细胞频率和hsa-miR-21-5p的上调是LC发展至HCC的独立危险因素。HCC中的单核细胞亚群分化与hsa-miR-21-5p和hsa-miR-155-5p有关。中间型单核细胞频率和hsa-miR-21-5p的组合上调可被视为LC发展至HCC的敏感指标。循环的中间型单核细胞和hsa-miR-21-5p是HCC进展的独立危险因素,临床和in silico验证。© 2023. 作者。
The authors aim to investigate the altered monocytes subsets distribution in liver cirrhosis (LC) and subsequent hepatocellular carcinoma (HCC) in association with the expression level of plasma Homo sapiens (has)-miR-21-5p and hsa-miR-155-5p. A step toward non-protein coding (nc) RNA precision medicine based on the immune perturbation manifested as altered monocytes distribution, on top of LC and HCC.Seventy-nine patients diagnosed with chronic hepatitis C virus (CHCV) infection with LC were enrolled in the current study. Patients were sub-classified into LC group without HCC (n = 40), LC with HCC (n = 39), and 15 apparently healthy controls. Monocyte subsets frequencies were assessed by flow cytometry. Real-time quantitative PCR was used to measure plasma hsa-miR-21-5p and hsa-miR-155-5p expression.Hsa-miR-21-5p correlated with intermediate monocytes (r = 0.30, p = 0.007), while hsa-miR-155-5p negatively correlated with non-classical monocytes (r = - 0.316, p = 0.005). ROC curve analysis revealed that combining intermediate monocytes frequency and hsa-miR-21 yielded sensitivity = 79.5%, specificity = 75%, and AUC = 0.84. In comparison, AFP yielded a lower sensitivity = 69% and 100% specificity with AUC = 0.85. Logistic regression analysis proved that up-regulation of intermediate monocytes frequency and hsa-miR-21-5p were independent risk factors for LC progression to HCC, after adjustment for co-founders.Monocyte subsets differentiation in HCC was linked to hsa-miR-21-5p and hsa-miR-155-5p. Combined up-regulation of intermediate monocytes frequency and hsa-miR-21-5p expression could be considered a sensitive indicator of LC progression to HCC. Circulating intermediate monocytes and hsa-miR-21-5p were independent risk factors for HCC evolution, clinically and in silico proved.© 2023. The Author(s).