Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors
As new biomarkers, circular RNAs (circRNAs) have been largely unexplored in prostate cancer (PCa). Using an integrative approach, we aimed to evaluate the potential of circRNAs and their linear transcripts (linRNAs) to act as (i) diagnostic biomarkers for differentiation between normal and tumor tis...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/7812 |
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| author | Hannah Rochow Monika Jung Sabine Weickmann Bernhard Ralla Carsten Stephan Sefer Elezkurtaj Ergin Kilic Zhongwei Zhao Klaus Jung Annika Fendler Antonia Franz |
| author_facet | Hannah Rochow Monika Jung Sabine Weickmann Bernhard Ralla Carsten Stephan Sefer Elezkurtaj Ergin Kilic Zhongwei Zhao Klaus Jung Annika Fendler Antonia Franz |
| author_sort | Hannah Rochow |
| collection | DOAJ |
| description | As new biomarkers, circular RNAs (circRNAs) have been largely unexplored in prostate cancer (PCa). Using an integrative approach, we aimed to evaluate the potential of circRNAs and their linear transcripts (linRNAs) to act as (i) diagnostic biomarkers for differentiation between normal and tumor tissue and (ii) prognostic biomarkers for the prediction of biochemical recurrence (BCR) after radical prostatectomy. In a first step, eight circRNAs (circ<i>ATXN10</i>, circ<i>CRIM1</i>, circ<i>CSNK1G3</i>, circ<i>GUCY1A2</i>, circ<i>LPP</i>, circ<i>NEAT1</i>, circ<i>RHOBTB3</i>, and circ<i>STIL</i>) were identified as differentially expressed via a genome-wide circRNA-based microarray analysis of six PCa samples. Additional bioinformatics and literature data were applied for this selection process. In total, 115 malignant PCa and 79 adjacent normal tissue samples were examined using robust RT-qPCR assays specifically established for the circRNAs and their linear counterparts. Their diagnostic and prognostic potential was evaluated using receiver operating characteristic curves, Cox regressions, decision curve analyses, and C-statistic calculations of prognostic indices. The combination of circ<i>ATXN10</i> and lin<i>STIL</i> showed a high discriminative ability between malignant and adjacent normal tissue PCa. The combination of lin<i>GUCY1A2</i>, lin<i>NEAT1</i>, and lin<i>STIL</i> proved to be the best predictive RNA-signature for BCR. The combination of this RNA signature with five established reference models based on only clinicopathological factors resulted in an improved predictive accuracy for BCR in these models. This is an encouraging study for PCa to evaluate circRNAs and their linRNAs in an integrative approach, and the results showed their clinical potential in combination with standard clinicopathological variables. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:25:15Z |
| publishDate | 2020-10-01 |
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| spelling | doaj.art-070a812306f6413ca7c0ca0dd1e411682023-11-20T18:02:49ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121781210.3390/ijms21217812Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological FactorsHannah Rochow0Monika Jung1Sabine Weickmann2Bernhard Ralla3Carsten Stephan4Sefer Elezkurtaj5Ergin Kilic6Zhongwei Zhao7Klaus Jung8Annika Fendler9Antonia Franz10Department of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Pathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Pathology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDepartment of Urology, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyAs new biomarkers, circular RNAs (circRNAs) have been largely unexplored in prostate cancer (PCa). Using an integrative approach, we aimed to evaluate the potential of circRNAs and their linear transcripts (linRNAs) to act as (i) diagnostic biomarkers for differentiation between normal and tumor tissue and (ii) prognostic biomarkers for the prediction of biochemical recurrence (BCR) after radical prostatectomy. In a first step, eight circRNAs (circ<i>ATXN10</i>, circ<i>CRIM1</i>, circ<i>CSNK1G3</i>, circ<i>GUCY1A2</i>, circ<i>LPP</i>, circ<i>NEAT1</i>, circ<i>RHOBTB3</i>, and circ<i>STIL</i>) were identified as differentially expressed via a genome-wide circRNA-based microarray analysis of six PCa samples. Additional bioinformatics and literature data were applied for this selection process. In total, 115 malignant PCa and 79 adjacent normal tissue samples were examined using robust RT-qPCR assays specifically established for the circRNAs and their linear counterparts. Their diagnostic and prognostic potential was evaluated using receiver operating characteristic curves, Cox regressions, decision curve analyses, and C-statistic calculations of prognostic indices. The combination of circ<i>ATXN10</i> and lin<i>STIL</i> showed a high discriminative ability between malignant and adjacent normal tissue PCa. The combination of lin<i>GUCY1A2</i>, lin<i>NEAT1</i>, and lin<i>STIL</i> proved to be the best predictive RNA-signature for BCR. The combination of this RNA signature with five established reference models based on only clinicopathological factors resulted in an improved predictive accuracy for BCR in these models. This is an encouraging study for PCa to evaluate circRNAs and their linRNAs in an integrative approach, and the results showed their clinical potential in combination with standard clinicopathological variables.https://www.mdpi.com/1422-0067/21/21/7812prostate cancermicroarrayidentificationvalidation and differential expression of circular RNAscircular RNAs and linear counterpartsbiochemical recurrence |
| spellingShingle | Hannah Rochow Monika Jung Sabine Weickmann Bernhard Ralla Carsten Stephan Sefer Elezkurtaj Ergin Kilic Zhongwei Zhao Klaus Jung Annika Fendler Antonia Franz Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors International Journal of Molecular Sciences prostate cancer microarray identification validation and differential expression of circular RNAs circular RNAs and linear counterparts biochemical recurrence |
| title | Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors |
| title_full | Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors |
| title_fullStr | Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors |
| title_full_unstemmed | Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors |
| title_short | Circular RNAs and Their Linear Transcripts as Diagnostic and Prognostic Tissue Biomarkers in Prostate Cancer after Prostatectomy in Combination with Clinicopathological Factors |
| title_sort | circular rnas and their linear transcripts as diagnostic and prognostic tissue biomarkers in prostate cancer after prostatectomy in combination with clinicopathological factors |
| topic | prostate cancer microarray identification validation and differential expression of circular RNAs circular RNAs and linear counterparts biochemical recurrence |
| url | https://www.mdpi.com/1422-0067/21/21/7812 |
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