Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma
Owing to the diagnostic dilemma, the prognosis of hepatocellular carcinoma (HCC) remains impoverished, contributing to the globally high mortality rate. Currently, HCC diagnosis depends on the combination of imaging modalities and the measurement of serum alpha-fetoprotein (AFP) levels. Nevertheless...
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| Format: | Article |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.929787/full |
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| author | Tahira Yousuf Tahira Yousuf Sadaf Bashir Dar Sadaf Ali Bangri Naseer A. Choh Zubaida Rasool Altaf Shah Rafiq Ahmed Rather Bilal Rah Gh Rasool Bhat Shazia Ali Dil Afroze Dil Afroze |
| author_facet | Tahira Yousuf Tahira Yousuf Sadaf Bashir Dar Sadaf Ali Bangri Naseer A. Choh Zubaida Rasool Altaf Shah Rafiq Ahmed Rather Bilal Rah Gh Rasool Bhat Shazia Ali Dil Afroze Dil Afroze |
| author_sort | Tahira Yousuf |
| collection | DOAJ |
| description | Owing to the diagnostic dilemma, the prognosis of hepatocellular carcinoma (HCC) remains impoverished, contributing to the globally high mortality rate. Currently, HCC diagnosis depends on the combination of imaging modalities and the measurement of serum alpha-fetoprotein (AFP) levels. Nevertheless, these conventional modalities exhibit poor performance in detecting HCC at early stages. Thus, there is a pressing need to identify novel circulating biomarkers to promote diagnostic accuracy and surveillance. Circulating miRNAs are emerging as promising diagnostic tools in screening various cancers, including HCC. However, because of heterogenous and, at times, contradictory reports, the universality of miRNAs in clinical settings remains elusive. Consequently, we proposed to explore the diagnostic potential of ten miRNAs selected on a candidate-based approach in HCC diagnosis. The expression of ten candidate miRNAs (Let-7a, miR-15a, miR-26a, miR-124, miR-126, miR-155, miR-219, miR-221, miR-222, and miR-340) was investigated in serum and tissue of 66 subjects, including 33 HCC patients and 33 healthy controls (HC), by rt-PCR. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic accuracy of the prospective serum miRNA panel. To anticipate the potential biological roles of a three-miRNA signature, the target genes were evaluated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway. The serum and tissue expression of miRNAs (Let-7a, miR-26a, miR-124, miR-155, miR-221, miR-222, and miR-340) were differentially expressed in HCC patients (p < 0.05). The ROC analysis revealed promising diagnostic performance of Let-7a (AUC = 0.801), miR-221 (AUC = 0.786), and miR-2 (AUC = 0.758) in discriminating HCC from HC. Furthermore, in a logistic regression equation, we identified a three-miRNA panel (Let-7a, miR-221, and miR-222; AUC = 0.932) with improved diagnostic efficiency in differentiating HCC from HC. Remarkably, the combination of AFP and a three-miRNA panel offered a higher accuracy of HCC diagnosis (AUC = 0.961) than AFP alone. The functional enrichment analysis demonstrated that target genes may contribute to pathways associated with HCC and cell-cycle regulation, indicating possible crosstalk of miRNAs with HCC development. To conclude, the combined classifier of a three-miRNA panel and AFP could be indispensable circulating biomarkers for HCC diagnosis. Furthermore, targeting predicted genes may provide new therapeutic clues for the treatment of aggressive HCC. |
| first_indexed | 2024-04-13T10:47:54Z |
| format | Article |
| id | doaj.art-5e3f2b100ff843a482af6410b54d257a |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T10:47:54Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-5e3f2b100ff843a482af6410b54d257a2022-12-22T02:49:45ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.929787929787Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinomaTahira Yousuf0Tahira Yousuf1Sadaf Bashir Dar2Sadaf Ali Bangri3Naseer A. Choh4Zubaida Rasool5Altaf Shah6Rafiq Ahmed Rather7Bilal Rah8Gh Rasool Bhat9Shazia Ali10Dil Afroze11Dil Afroze12Advance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaDepartment of Immunology and Molecular Medicine, SKIMS, Srinagar, Jammu and Kashmir, IndiaAdvance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaDepartment of Surgical Gastroenterology, SKIMS, Srinagar, Jammu and Kashmir, IndiaDepartment of Radio-Diagnosis, SKIMS, Srinagar, Jammu and Kashmir, IndiaDepartment of Pathology, SKIMS, Srinagar, Jammu and Kashmir, IndiaDepartment of Gastroenterology, SKIMS, Srinagar, Jammu and Kashmir, IndiaAdvance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaAdvance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaAdvance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaAdvance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaAdvance Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Srinagar, Jammu and Kashmir, IndiaDepartment of Immunology and Molecular Medicine, SKIMS, Srinagar, Jammu and Kashmir, IndiaOwing to the diagnostic dilemma, the prognosis of hepatocellular carcinoma (HCC) remains impoverished, contributing to the globally high mortality rate. Currently, HCC diagnosis depends on the combination of imaging modalities and the measurement of serum alpha-fetoprotein (AFP) levels. Nevertheless, these conventional modalities exhibit poor performance in detecting HCC at early stages. Thus, there is a pressing need to identify novel circulating biomarkers to promote diagnostic accuracy and surveillance. Circulating miRNAs are emerging as promising diagnostic tools in screening various cancers, including HCC. However, because of heterogenous and, at times, contradictory reports, the universality of miRNAs in clinical settings remains elusive. Consequently, we proposed to explore the diagnostic potential of ten miRNAs selected on a candidate-based approach in HCC diagnosis. The expression of ten candidate miRNAs (Let-7a, miR-15a, miR-26a, miR-124, miR-126, miR-155, miR-219, miR-221, miR-222, and miR-340) was investigated in serum and tissue of 66 subjects, including 33 HCC patients and 33 healthy controls (HC), by rt-PCR. Receiver operating characteristic curve (ROC) analysis was used to determine the diagnostic accuracy of the prospective serum miRNA panel. To anticipate the potential biological roles of a three-miRNA signature, the target genes were evaluated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway. The serum and tissue expression of miRNAs (Let-7a, miR-26a, miR-124, miR-155, miR-221, miR-222, and miR-340) were differentially expressed in HCC patients (p < 0.05). The ROC analysis revealed promising diagnostic performance of Let-7a (AUC = 0.801), miR-221 (AUC = 0.786), and miR-2 (AUC = 0.758) in discriminating HCC from HC. Furthermore, in a logistic regression equation, we identified a three-miRNA panel (Let-7a, miR-221, and miR-222; AUC = 0.932) with improved diagnostic efficiency in differentiating HCC from HC. Remarkably, the combination of AFP and a three-miRNA panel offered a higher accuracy of HCC diagnosis (AUC = 0.961) than AFP alone. The functional enrichment analysis demonstrated that target genes may contribute to pathways associated with HCC and cell-cycle regulation, indicating possible crosstalk of miRNAs with HCC development. To conclude, the combined classifier of a three-miRNA panel and AFP could be indispensable circulating biomarkers for HCC diagnosis. Furthermore, targeting predicted genes may provide new therapeutic clues for the treatment of aggressive HCC.https://www.frontiersin.org/articles/10.3389/fgene.2022.929787/fullcirculating miRNAbiomarkerdiagnosistherapeuticshepatocellular carcinoma |
| spellingShingle | Tahira Yousuf Tahira Yousuf Sadaf Bashir Dar Sadaf Ali Bangri Naseer A. Choh Zubaida Rasool Altaf Shah Rafiq Ahmed Rather Bilal Rah Gh Rasool Bhat Shazia Ali Dil Afroze Dil Afroze Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma Frontiers in Genetics circulating miRNA biomarker diagnosis therapeutics hepatocellular carcinoma |
| title | Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma |
| title_full | Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma |
| title_fullStr | Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma |
| title_full_unstemmed | Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma |
| title_short | Diagnostic implication of a circulating serum-based three-microRNA signature in hepatocellular carcinoma |
| title_sort | diagnostic implication of a circulating serum based three microrna signature in hepatocellular carcinoma |
| topic | circulating miRNA biomarker diagnosis therapeutics hepatocellular carcinoma |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.929787/full |
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