El-Khazragy Nashwa, Elshimy Amal Ali, Hassan Safaa Shawky, Shaaban Mohamed Hafez, Bayoumi Ahmed Hamed, El Magdoub Hekmat M, Ghozy Sherief, Gaballah Ahmed, Aboelhussein Marwa M, Abou Gabal Hoda H, Bannunah Azzah M, Mansy Azza El-Sayed
Department of Clinical Pathology-Hematology, and Ain Shams Medical Research Institute (MASRI), Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Department of Medical Microbiology and Immunology, Faculty of Medicine, Cairo University and Galala University, Cairo, Egypt.
Mol Carcinog. 2020 Dec;59(12):1382-1391. doi: 10.1002/mc.23263. Epub 2020 Oct 19.
Emerging hepatocellular carcinoma (HCC) has been sequentially reported in chronic hepatitis C virus (HCV) treated with direct-acting antivirals (DAAs). Homeobox transcript antisense RNA (HOTAIR), an oncogene, has been reported to be associated with cancer. We investigated the predictive value of lnc-HOTAIR for HCC surveillance in chronic HCV patients following DAAs therapy. The expression levels of lnc-HOTAIR and ATG-7 genes were measured in 220 with chronic HCV, following a DAAs based therapy for 12 weeks, the patients were followed-up for attentive surveillance of HCC for 12 months after starting DAAs. In terms of lnc-HOTAIR, patients with HCC and high viral load had significantly higher median expression levels of HOTAIR of (68 vs. 24; p = .001) and (94 vs. 52; p = .001), respectively. Moreover, the median expression level of ATG-7 was higher in those who developed HCC (114 vs. 51; p = .001). The expression of lnc-HOTAIR and ATG-7 are significant predictors of the development of HCC in HCV-4 infected patients treated with DAAs, with a cut-off value of 37 and 86, respectively. The increased expression levels of lnc-HOTAIR more than 68 in HCC patients following DAAs were correlated with poorer disease outcomes compared to those with lower expression levels; however, ATG-7 expression levels more than 114 were correlated with worse overall survival but not the progression-free one. We suggest that high expression levels of lnc-HOTAIR could serve as a risk assessment biomarker for HCC before and during DAAs course therapy in Chronic HCV-4 patients, and should be rigorously taken into consideration before DAAs.
在接受直接作用抗病毒药物(DAA)治疗的慢性丙型肝炎病毒(HCV)患者中,陆续有新发肝细胞癌(HCC)的报道。同源盒转录反义RNA(HOTAIR)作为一种致癌基因,已被报道与癌症相关。我们研究了lnc-HOTAIR在DAA治疗后的慢性HCV患者HCC监测中的预测价值。在220例慢性HCV患者中测量lnc-HOTAIR和ATG-7基因的表达水平,在基于DAA的治疗12周后,患者在开始DAA治疗后接受12个月的HCC密切监测。就lnc-HOTAIR而言,HCC患者和高病毒载量患者的HOTAIR中位表达水平分别显著更高(68对24;p = 0.001)和(94对52;p = 0.001)。此外,发生HCC的患者中ATG-7的中位表达水平更高(114对51;p = 0.001)。lnc-HOTAIR和ATG-7的表达是接受DAA治疗的HCV-4感染患者发生HCC的重要预测指标,截断值分别为37和86。与低表达水平的患者相比,DAA治疗后HCC患者中lnc-HOTAIR表达水平超过68与较差的疾病结局相关;然而,ATG-7表达水平超过114与较差的总生存期相关,但与无进展生存期无关。我们认为,lnc-HOTAIR的高表达水平可作为慢性HCV-4患者在DAA疗程治疗前和治疗期间HCC的风险评估生物标志物,在使用DAA之前应予以严格考虑。