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Long non-coding RNA HOTAIR and HOTTIP as potential biomarkers for hepatitis C virus genotype 4-induced hepatocellular carcinoma
Egyptian Journal of Medical Human Genetics Pub Date : 2020-02-20 , DOI: 10.1186/s43042-020-0048-8
Fawzy Roshdy , Mohamed M. S. Farag , Eman El-Ahwany , Ola Mahmode , Adel A. Mousa , Mohamed El Talkawy , Faiza Essawy

Long non-coding RNAs (lncRNAs) homeobox (Hox) transcript antisense intergenic RNA (HOTAIR) and HOXA transcript at the distal tip (HOTTIP) have been suggested to be implicated in liver cancer tumorigenesis and progression; however, little is known about the role of the plasma HOTAIR and HOTTIP in liver cancer diagnosis and prognosis. The current study aimed at measuring the plasma levels of long non-coding RNAs (HOTAIR and HOTTIP) expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients in an attempt to evaluate the potential benefits of these new circulating as non-invasive diagnostic biomarkers and a novel therapeutic strategy for liver cirrhosis and carcinogenesis of Egyptian patients. Hundred subjects were included in this study, divided into two groups; group I (50 patients) were classified into subgroup Ia (CLD without cirrhosis, n = 25) and subgroup Ib (CLD with cirrhosis, n = 25), group II (CLD patients with HCC, n = 25), and control (healthy volunteer, n = 25). The expression of lncRNAs (HOTAIR and HOTTIP) genes was analyzed by real-time PCR. LncRNAs (HOTAIR and HOTTIP) showed upregulation in all diseased groups, which was in consistent with the progression of the disease toward the HCC stage. In addition, HOTAIR and HOTTIP showed a diagnostic ability to discriminate between cases of cirrhosis and HCC compared with healthy control (p < 0.001), while HOTAIR and HOTTIP did not show a discrimination significant differences between cirrhotic cases and non-cirrhotic cases. By using receiver operating characteristic curve (ROC) analysis, it was found that LncRNAs (HOTAIR and HOTTIP) could diagnose liver cancer with 64.0% sensitivity and 86.0% specificity and 48.0% sensitivity and 88.0% specificity. Furthermore, both genes can be considered as the predictor and prognostic parameters for cirrhosis (OR = 1.111, p = 0.05) and (OR = 1.07, p = 0.05) respectively, and HCC (OR = 1.047, p = 0.01) and (OR = 1.05, p = 0.003). The increased HOTAIR and HOTTIP expression were associated with advanced tumor stages and higher grades. These results strongly prompt us that HOTAIR and HOTTIP genes can be used as non-invasive prognostic biomarkers and new therapeutic targets for HCV genotype 4-induced HCC.

中文翻译:

长链非编码 RNA HOTAIR 和 HOTTIP 作为丙型肝炎病毒基因型 4 诱导的肝细胞癌的潜在生物标志物

长链非编码 RNA (lncRNA) 同源盒 (Hox) 转录反义基因间 RNA (HOTAIR) 和远端 HOXA 转录 (HOTTIP) 已被认为与肝癌肿瘤的发生和进展有关。然而,关于血浆 HOTAIR 和 HOTTIP 在肝癌诊断和预后中的作用知之甚少。目前的研究旨在测量因 HCV 基因 4 型感染伴/不伴肝硬化和 HCC 的慢性肝病 (CLD) 中长链非编码 RNA(HOTAIR 和 HOTTIP)表达的血浆水平,以试图评估这些新的循环作为非侵入性诊断生物标志物和埃及患者肝硬化和癌变的新治疗策略。本次研究共纳入一百名受试者,分为两组;I组(50例患者)分为Ia亚组(无肝硬化的CLD,n=25)和Ib亚组(伴肝硬化的CLD,n=25)、II组(伴HCC的CLD患者,n=25)和对照组(健康志愿者,n = 25)。通过实时 PCR 分析 lncRNA(HOTAIR 和 HOTTIP)基因的表达。LncRNA(HOTAIR 和 HOTTIP)在所有患病组中均表现出上调,这与疾病向 HCC 阶段的进展一致。此外,与健康对照相比,HOTAIR 和 HOTTIP 显示出区分肝硬化和 HCC 病例的诊断能力(p < 0.001),而 HOTAIR 和 HOTTIP 未显示出区分肝硬化病例和非肝硬化病例的显着差异。通过使用接收者操作特征曲线(ROC)分析,发现LncRNAs(HOTAIR和HOTTIP)可以以64.0%的敏感性和86.0%的特异性和48.0%的敏感性和88.0%的特异性诊断肝癌。此外,这两个基因可以分别被视为肝硬化 (OR = 1.111, p = 0.05) 和 (OR = 1.07, p = 0.05) 和 HCC (OR = 1.047, p = 0.01) 和 (OR = 1.05,p = 0.003)。增加的 HOTAIR 和 HOTTIP 表达与晚期肿瘤分期和更高级别相关。这些结果强烈提示我们,HOTAIR 和 HOTTIP 基因可用作 HCV 基因型 4 诱导的 HCC 的非侵入性预后生物标志物和新的治疗靶点。这两个基因可以分别被视为肝硬化 (OR = 1.111, p = 0.05) 和 (OR = 1.07, p = 0.05) 和 HCC (OR = 1.047, p = 0.01) 和 (OR = 1.05) 的预测因子和预后参数, p = 0.003)。增加的 HOTAIR 和 HOTTIP 表达与晚期肿瘤分期和更高级别相关。这些结果强烈提示我们,HOTAIR 和 HOTTIP 基因可用作 HCV 基因型 4 诱导的 HCC 的非侵入性预后生物标志物和新的治疗靶点。这两个基因可以分别被视为肝硬化 (OR = 1.111, p = 0.05) 和 (OR = 1.07, p = 0.05) 和 HCC (OR = 1.047, p = 0.01) 和 (OR = 1.05) 的预测因子和预后参数, p = 0.003)。增加的 HOTAIR 和 HOTTIP 表达与晚期肿瘤分期和更高级别相关。这些结果强烈提示我们,HOTAIR 和 HOTTIP 基因可用作 HCV 基因型 4 诱导的 HCC 的非侵入性预后生物标志物和新的治疗靶点。
更新日期:2020-02-20
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