TY - JOUR
T1 - MicroRNA-based signatures impacting clinical course and biology of ovarian cancer: a miRNOmics study
AU - Krasniqi, E.
AU - Sacconi, A.
AU - Marinelli, D.
AU - Pizzuti, L.
AU - Mazzotta, M.
AU - Sergi, D.
AU - Capomolla, E.
AU - Donzelli, S.
AU - Carosi, M.
AU - Bagnato, A.
AU - Gamucci, T.
AU - Tomao, S.
AU - Natoli, C.
AU - Marchetti, P.
AU - Grassadonia, A.
AU - Tinari, N.
AU - De Tursi, M.
AU - Vizza, E.
AU - Ciliberto, G.
AU - Landi, L.
AU - Cappuzzo, F.
AU - Barba, M.
AU - Blandino, G.
AU - Vici, P.
N1 - Funding Information:
SA, MD, MM, SD, CE, DS, CM, BA, TS, GA, TN, DTM, VE, CG, LL, CF, BM, and BG declare no conflicts of interest. KE received fees for scientific advice for Eisai and Novartis. PL received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees from Roche, Pfizer, Novartis, Gentili. MP had an advisory role for BMS, Roche Genentech, MSD, Novartis, Amgen, Merck Serono, Pierre Fabre, and Incyte. GT received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, Lilly. NC received travel grants/personal fees from Pfizer, EISAI, Novartis, Merck Sharp & Dohme, AstraZeneca. VP received travel grants from Eisai, Roche, Pfizer, Novartis; speaker fees/advisory boards from Roche, Pfizer, Novartis, Gentili, Lilly.
Funding Information:
This study was partly financed by an intramural grant awarded by the scientific direction of the Regina Elena National Cancer Institute.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. Methods: We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). Results: In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Conclusions: Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.
AB - Background: In Western countries, ovarian cancer (OC) still represents the leading cause of gynecological cancer-related deaths, despite the remarkable gains in therapeutical options. Novel biomarkers of early diagnosis, prognosis definition and prediction of treatment outcomes are of pivotal importance. Prior studies have shown the potentials of micro-ribonucleic acids (miRNAs) as biomarkers for OC and other cancers. Methods: We focused on the prognostic and/or predictive potential of miRNAs in OC by conducting a comprehensive array profiling of miRNA expression levels in ovarian tissue samples from 17 non-neoplastic controls, and 60 tumor samples from OC patients treated at the Regina Elena National Cancer Institute (IRE). A set of 54 miRNAs with differential expression in tumor versus normal samples (T/N-deregulated) was identified in the IRE cohort and validated against data from the Cancer Genoma Atlas (TCGA) related to 563 OC patients and 8 non-neoplastic controls. The prognostic/predictive role of the selected 54 biomarkers was tested in reference to survival endpoints and platinum resistance (P-res). Results: In the IRE cohort, downregulation of the 2 miRNA-signature including miR-99a-5p and miR-320a held a negative prognostic relevance, while upregulation of miR-224-5p was predictive of less favorable event free survival (EFS) and P-res. Data from the TCGA showed that downregulation of 5 miRNAs, i.e., miR-150, miR-30d, miR-342, miR-424, and miR-502, was associated with more favorable EFS and overall survival outcomes, while miR-200a upregulation was predictive of P-res. The 9 miRNAs globally identified were all included into a single biologic signature, which was tested in enrichment analysis using predicted/validated miRNA target genes, followed by network representation of the miRNA-mRNA interactions. Conclusions: Specific dysregulated microRNA sets in tumor tissue showed predictive/prognostic value in OC, and resulted in a promising biological signature for this disease.
KW - miRNAs
KW - Ovarian cancer
KW - Prognostic/predictive biomarkers
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U2 - 10.1186/s40364-021-00289-6
DO - 10.1186/s40364-021-00289-6
M3 - Article
AN - SCOPUS:85109858672
SN - 2050-7771
VL - 9
JO - Biomarker Research
JF - Biomarker Research
IS - 1
M1 - 57
ER -