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Open AccessArticle

Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma

1
Fondazione Italiana Fegato-ONLUS, Area Science Park, ss14, km163.5, 34149 Trieste, Italy
2
Faculty of Medicine, Universitas Hasanuddin, Makassar 90245, Indonesia
3
Dipartemento di Scienze della Vita, Università degli Studi di Trieste, 34149 Trieste, Italy
4
Department of Medical Sciences, University of Trieste, 34149 Trieste, Italy
5
Clinica Patologie Fegato, Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Via Giovanni Sai 7, 34149 Trieste, Italy
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(10), 2810; https://doi.org/10.3390/cancers12102810
Received: 27 August 2020 / Revised: 21 September 2020 / Accepted: 24 September 2020 / Published: 29 September 2020
(This article belongs to the Section Cancer Biomarkers)
In the present study, we identified new prognostic serum miRNA biomarkers to predict therapy response and disease-free survival according to different therapeutic strategies in hepatocellular carcinoma (HCC). MiR-4443, miR-4454, and miR-4530 were significantly related to treatment response to HCC curative treatments (liver resection and radiofrequency ablation) while miR-4492 was related to treatment response of trans-arterial chemoembolization (TACE). The value of these results can contribute to setting the basis for personalized medicine for HCC patients and to improve the survival of HCC patients in the future.
The clinical outcome of hepatocellular carcinoma (HCC) treatment remains unsatisfactory, contributing to the high mortality of HCC worldwide. Circulating miRNAs have the potential to be a predictor of therapy response. Microarray profiling was performed in serum samples of 20 HCC patients before treatment. Circulating miRNAs associated with treatment response were validated in 86 serum HCC samples using the qRT-PCR system. Patients were treated either with curative treatments (resection or radiofrequency) or trans-arterial chemoembolization (TACE), and grouped according to therapy response in complete responders (CR) and partial responders or progressive disease (PRPD), following mRECIST criteria. Four miRNA candidates from the discovery phase (miR-4443, miR-4454, miR-4492, and miR-4530) were validated. Before therapy, miR-4454 and miR-4530 were up-regulated in CR to curative treatments (2.83 fold, p = 0.02 and 2.33 fold, p = 0.008, respectively) and were able to differentiate CR from PRPD (area under the curve (AUC) = 0.74, sens/spec 79/63% and AUC = 0.77, sens/spec 72/73%). On the contrary, miR-4443 was 1.95 times down-regulated in CR (p = 0.05) with an AUC of 0.72 (sens = 70%, spec = 60%) in distinguishing CR vs. PRPD. The combination of the three miRNAs was able to predict the response to curative treatment with an AUC of 0.84 (sens = 72%, spec = 75%). The higher levels of miR-4454 and miR-4530 in were associated to longer overall survival (HR = 2.79, p = 0.029 and HR = 2.97, p = 0.011, respectively). Before TACE, miR-4492 was significantly up-regulated in CR patients (FC = 2.67, p = 0.01) and able to differentiate CR from PRPD (AUC = 0.84, sens/spec 84.6/71%). We demonstrated that different miRNAs predictors can be used as potential prognostic circulating biomarkers according to the selected treatment for HCC. View Full-Text
Keywords: non-coding RNA; serum biomarker; TACE; radiofrequency ablation; liver tumor non-coding RNA; serum biomarker; TACE; radiofrequency ablation; liver tumor
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MDPI and ACS Style

Pratama, M.Y.; Visintin, A.; Crocè, L.S.; Tiribelli, C.; Pascut, D. Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma. Cancers 2020, 12, 2810. https://doi.org/10.3390/cancers12102810

AMA Style

Pratama MY, Visintin A, Crocè LS, Tiribelli C, Pascut D. Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma. Cancers. 2020; 12(10):2810. https://doi.org/10.3390/cancers12102810

Chicago/Turabian Style

Pratama, Muhammad Y.; Visintin, Alessia; Crocè, Lory S.; Tiribelli, Claudio; Pascut, Devis. 2020. "Circulatory miRNA as a Biomarker for Therapy Response and Disease-Free Survival in Hepatocellular Carcinoma" Cancers 12, no. 10: 2810. https://doi.org/10.3390/cancers12102810

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