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索拉非尼治疗的肝癌患者中miR-23b-3p、miR-126-3p和lncRNA GAS5的纵向循环水平

Longitudinal Circulating Levels of miR-23b-3p, miR-126-3p and lncRNA GAS5 in HCC Patients Treated with Sorafenib.

作者信息

Manganelli Michele, Grossi Ilaria, Ferracin Manuela, Guerriero Paola, Negrini Massimo, Ghidini Michele, Senti Chiara, Ratti Margherita, Pizzo Claudio, Passalacqua Rodolfo, Molfino Sarah, Baiocchi Gianluca, Portolani Nazario, Marchina Eleonora, De Petro Giuseppina, Salvi Alessandro

机构信息

Department of Molecular and Translational Medicine, Division of Biology and Genetics, University of Brescia, 25123 Brescia, Italy.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40126 Bologna, Italy.

出版信息

Biomedicines. 2021 Jul 13;9(7):813. doi: 10.3390/biomedicines9070813.

Abstract

Human hepatocellular carcinoma (HCC) is the most frequent primary tumor of the liver and the third cause of cancer-related deaths. The multikinase inhibitor sorafenib is a systemic drug for unresectable HCC. The identification of molecular biomarkers for the early diagnosis of HCC and responsiveness to treatment are needed. In this work, we performed an exploratory study to investigate the longitudinal levels of cell-free long ncRNA GAS5 and microRNAs miR-126-3p and -23b-3p in a cohort of 7 patients during the period of treatment with sorafenib. We used qPCR to measure the amounts of GAS5 and miR-126-3p and droplet digital PCR (ddPCR) to measure the levels of miR-23b-3p. Patients treated with sorafenib displayed variable levels of GAS5, miR-126-3p and miR-23b-3p at different time-points of follow-up. miR-23b-3p was further measured by ddPCR in 37 healthy individuals and 25 untreated HCC patients. The amount of miR-23b-3p in the plasma of untreated HCC patients was significantly downregulated if compared to healthy individuals. The ROC curve analysis underlined its diagnostic relevance. In conclusion, our results highlight a potential clinical significance of circulating miR-23b-3p and an exploratory observation on the longitudinal plasmatic levels of GAS5, miR-126-3p and miR-23b-3p during sorafenib treatment.

摘要

人类肝细胞癌(HCC)是最常见的原发性肝癌,也是癌症相关死亡的第三大原因。多激酶抑制剂索拉非尼是一种用于不可切除HCC的全身性药物。需要鉴定用于HCC早期诊断和治疗反应性的分子生物标志物。在这项研究中,我们进行了一项探索性研究,以调查7例患者在索拉非尼治疗期间无细胞长链非编码RNA GAS5以及微小RNA miR-126-3p和-23b-3p的纵向水平。我们使用qPCR测量GAS5和miR-126-3p的量,并使用液滴数字PCR(ddPCR)测量miR-23b-3p的水平。接受索拉非尼治疗的患者在随访的不同时间点显示出不同水平的GAS5、miR-126-3p和miR-23b-3p。在37名健康个体和25名未治疗的HCC患者中,通过ddPCR进一步测量了miR-23b-3p。与健康个体相比,未治疗的HCC患者血浆中miR-23b-3p的量显著下调。ROC曲线分析强调了其诊断相关性。总之,我们的结果突出了循环miR-23b-3p的潜在临床意义,以及对索拉非尼治疗期间GAS5、miR-126-3p和miR-23b-3p纵向血浆水平的探索性观察。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5a28/8301380/886fbadb65bd/biomedicines-09-00813-g001.jpg

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