Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer
BackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study wa...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2021.667212/full |
| _version_ | 1818640023171366912 |
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| author | Haiming Huang Jialin Du Bo Jin Lu Pang Nan Duan Chenwei Huang Jiayin Hou Wei Yu Han Hao Haixia Li |
| author_facet | Haiming Huang Jialin Du Bo Jin Lu Pang Nan Duan Chenwei Huang Jiayin Hou Wei Yu Han Hao Haixia Li |
| author_sort | Haiming Huang |
| collection | DOAJ |
| description | BackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.MethodsRNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.ResultsRNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.ConclusionsThese findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa. |
| first_indexed | 2024-12-16T23:04:40Z |
| format | Article |
| id | doaj.art-d3a92587716749bb958c6fff1d79881f |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-16T23:04:40Z |
| publishDate | 2021-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-d3a92587716749bb958c6fff1d79881f2022-12-21T22:12:36ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-04-011110.3389/fonc.2021.667212667212Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder CancerHaiming Huang0Jialin Du1Bo Jin2Lu Pang3Nan Duan4Chenwei Huang5Jiayin Hou6Wei Yu7Han Hao8Haixia Li9Department of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaDepartment of Urology, Peking University First Hospital and Institute of Urology, Beijing, ChinaDepartment of Urology, Peking University First Hospital and Institute of Urology, Beijing, ChinaDepartment of Clinical Laboratory, Peking University First Hospital, Beijing, ChinaBackgroundThe recent discovery of miRNAs and lncRNAs in urine exosomes has emerged as promising diagnostic biomarkers for bladder cancer (BCa). However, mRNAs as the direct products of transcription has not been well evaluated in exosomes as biomarkers for BCa diagnosis. The purpose of this study was to identify tumor progression-related mRNAs and lncRNAs in urine exosomes that could be used for detection of BCa.MethodsRNA-sequencing was performed to identify tumor progression-related biomarkers in three matched superficial tumor and deep infiltrating tumor regions of muscle-invasive bladder cancer (MIBC) specimens, differently expressed mRNAs and lncRNAs were validated in TCGA dataset (n = 391) in the discovery stage. Then candidate RNAs were chosen for evaluation in urine exosomes of a training cohort (10 BCa and 10 healthy controls) and a validation cohort (80 BCa and 80 healthy controls) using RT-qPCR. The diagnostic potential of the candidates were evaluated by receiver operating characteristic (ROC) curves.ResultsRNA sequencing revealed 8 mRNAs and 32 lncRNAs that were significantly upregulated in deep infiltrating tumor region. After validation in TCGA database, 10 markedly dysregulated RNAs were selected for further investigation in urine exosomes, of which five (mRNAs: KLHDC7B, CASP14, and PRSS1; lncRNAs: MIR205HG and GAS5) were verified to be significantly dysregulated. The combination of the five RNAs had the highest AUC to disguising the BCa (0.924, 95% CI, 0.875–0.974) or early stage BCa patients (0.910, 95% CI, 0.850 to 0.971) from HCs. The expression levels of these five RNAs were correlated with tumor stage, grade, and hematuria degrees.ConclusionsThese findings highlight the potential of urine exosomal mRNAs and lncRNAs profiling in the early diagnosis and provide new insights into the molecular mechanisms involved in BCa.https://www.frontiersin.org/articles/10.3389/fonc.2021.667212/fullurine exosomesmRNAlncRNAnon-invasive biomarkersdiagnosisbladder cancer |
| spellingShingle | Haiming Huang Jialin Du Bo Jin Lu Pang Nan Duan Chenwei Huang Jiayin Hou Wei Yu Han Hao Haixia Li Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer Frontiers in Oncology urine exosomes mRNA lncRNA non-invasive biomarkers diagnosis bladder cancer |
| title | Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer |
| title_full | Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer |
| title_fullStr | Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer |
| title_full_unstemmed | Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer |
| title_short | Combination of Urine Exosomal mRNAs and lncRNAs as Novel Diagnostic Biomarkers for Bladder Cancer |
| title_sort | combination of urine exosomal mrnas and lncrnas as novel diagnostic biomarkers for bladder cancer |
| topic | urine exosomes mRNA lncRNA non-invasive biomarkers diagnosis bladder cancer |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2021.667212/full |
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