Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer
Abstract Background Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-bio...
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| Format: | Article |
| Language: | English |
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BMC
2022-02-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-022-01527-7 |
| _version_ | 1819274845699964928 |
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| author | Souvick Roy Mitsuro Kanda Sachiyo Nomura Zhongxu Zhu Yuji Toiyama Akinobu Taketomi James Goldenring Hideo Baba Yasuhiro Kodera Ajay Goel |
| author_facet | Souvick Roy Mitsuro Kanda Sachiyo Nomura Zhongxu Zhu Yuji Toiyama Akinobu Taketomi James Goldenring Hideo Baba Yasuhiro Kodera Ajay Goel |
| author_sort | Souvick Roy |
| collection | DOAJ |
| description | Abstract Background Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC. Methods We performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies. Results We identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation. Conclusions We identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC. |
| first_indexed | 2024-12-23T23:14:54Z |
| format | Article |
| id | doaj.art-6dc20b27d59e46398e7d46ed80f545e4 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-23T23:14:54Z |
| publishDate | 2022-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-6dc20b27d59e46398e7d46ed80f545e42022-12-21T17:26:31ZengBMCMolecular Cancer1476-45982022-02-0121111210.1186/s12943-022-01527-7Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancerSouvick Roy0Mitsuro Kanda1Sachiyo Nomura2Zhongxu Zhu3Yuji Toiyama4Akinobu Taketomi5James Goldenring6Hideo Baba7Yasuhiro Kodera8Ajay Goel9Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of HopeDepartment of Gastroenterological Surgery, Nagoya University Graduate School of MedicineDepartment of Gastrointestinal Surgery, Graduate School of Medicine, The University of TokyoDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of HopeDepartment of Gastrointestinal and Pediatric Surgery, Division of Reparative Medicine, Institute of Life Sciences, Mie University Graduate School of MedicineDepartment of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido UniversitySection of Surgical Sciences, Department of Cell and Developmental Biology, Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville VA Medical CenterDepartment of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Gastroenterological Surgery, Nagoya University Graduate School of MedicineDepartment of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of HopeAbstract Background Majority of gastric cancers (GC) are diagnosed at advanced stages which contributes towards their poor prognosis. In view of this clinical challenge, identification of non-invasive biomarker for early diagnosis is imperative. Herein, we aimed to develop a non-invasive, liquid-biopsy based assay by using circular RNAs (circRNAs) as molecular biomarkers for early detection of GC. Methods We performed systematic biomarker discovery and validation of the candidate circRNAs in matched tissue specimens of GC and adjacent normal mucosa. Next, we translated the discovered circRNA based biomarker panel into serum samples in a training and validation cohort of GC patients (n = 194) and non-disease controls (n = 94) and evaluated their diagnostic performance. In addition, we measured the expression of circRNAs in serum samples of pre- and post-surgical GC patients and evaluated the specificity of circRNAs biomarker panel with respect to other gastro-intestinal (GI) malignancies. Results We identified 10-circRNAs in the discovery phase with subsequent validation in a pilot cohort of GC tissue specimens. Using a training cohort of patients, we developed an 8-circRNA based risk-prediction model for the diagnosis of GC. We observed that our biomarker panel robustly discriminated GC patients from non-disease controls with an AUC of 0.87 in the training, and AUC of 0.83 in the validation cohort. Notably, the biomarker panel could robustly identify even early-stage GC patients, regardless of their tumor histology (diffuse vs. intestinal). The decreased expression of circRNAs in post-surgery serum specimens indicated their tumor-specificity and their potential source of origin in the systemic circulation. Conclusions We identified a panel of 8-circRNAs as non-invasive, liquid-biopsy biomarkers which might serve as potential diagnostic biomarkers for the early detection of GC.https://doi.org/10.1186/s12943-022-01527-7Circular RNAsGastric cancerBiomarker panelNon-invasive liquid-biopsy assay |
| spellingShingle | Souvick Roy Mitsuro Kanda Sachiyo Nomura Zhongxu Zhu Yuji Toiyama Akinobu Taketomi James Goldenring Hideo Baba Yasuhiro Kodera Ajay Goel Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer Molecular Cancer Circular RNAs Gastric cancer Biomarker panel Non-invasive liquid-biopsy assay |
| title | Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer |
| title_full | Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer |
| title_fullStr | Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer |
| title_full_unstemmed | Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer |
| title_short | Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer |
| title_sort | diagnostic efficacy of circular rnas as noninvasive liquid biopsy biomarkers for early detection of gastric cancer |
| topic | Circular RNAs Gastric cancer Biomarker panel Non-invasive liquid-biopsy assay |
| url | https://doi.org/10.1186/s12943-022-01527-7 |
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