A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study

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dc.contributor.authorMiyoshi, Jinsei
dc.contributor.authorZhu, Zhongxu
dc.contributor.authorLuo, Aiping
dc.contributor.authorToden, Shusuke
dc.contributor.authorZhou, Xuantong
dc.contributor.authorIzumi, Daisuke
dc.contributor.authorKanda, Mitsuro
dc.contributor.authorTakayama, Tetsuji
dc.contributor.authorParker, Iqbal M
dc.contributor.authorWang, Minjie
dc.contributor.authorGao, Feng
dc.contributor.authorZaidi, Ali H
dc.contributor.authorBaba, Hideo
dc.contributor.authorKodera, Yasuhiro
dc.contributor.authorCui, Yongping
dc.contributor.authorWang, Xin
dc.contributor.authorLiu, Zhihua
dc.contributor.authorGoel, Ajay
dc.date.accessioned2022-04-09T08:08:01Z
dc.date.available2022-04-09T08:08:01Z
dc.date.issued2022-02-11
dc.date.updated2022-02-14T07:35:20Z
dc.description.abstractBackground Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis. Methods We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR. Using a serum training cohort (n = 408), we conducted multivariate logistic regression analysis to develop an ESCC circulating miRNA signature and the signature was subsequently validated in two independent retrospective and two prospective cohorts. Results We identified eighteen initial miRNA candidates from three miRNA expression datasets (n = 108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confirmed the overexpression of 8 miRNAs (miR-103, miR-106b, miR-151, miR-17, miR-181a, miR-21, miR-25, and miR-93) in serum specimens. Using a serum training cohort, we developed a circulating miRNA signature (AUC:0.83 [95%CI:0.79–0.87]) and the diagnostic performance of the miRNA signature was confirmed in two independent validation cohorts (n = 126, AUC:0.80 [95%CI:0.69–0.91]; and n = 165, AUC:0.89 [95%CI:0.83–0.94]). Finally, we demonstrated the diagnostic performance of the 8-miRNA signature in two prospective cohorts (n = 185, AUC:0.92, [95%CI:0.87–0.96]); and (n = 188, AUC:0.93, [95%CI:0.88–0.97]). Importantly, the 8-miRNA signature was superior to current clinical serological markers in discriminating early stage ESCC patients from healthy controls (p < 0.001). Conclusions We have developed a novel and robust circulating miRNA-based signature for early detection of ESCC, which was successfully validated in multiple retrospective and prospective multinational, multicenter cohorts.en_US
dc.identifier.apacitationMiyoshi, J., Zhu, Z., Luo, A., Toden, S., Zhou, X., Izumi, D., ... Goel, A. (2022). A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. <i>Molecular Cancer</i>, 21(1), 44. http://hdl.handle.net/11427/36311en_ZA
dc.identifier.chicagocitationMiyoshi, Jinsei, Zhongxu Zhu, Aiping Luo, Shusuke Toden, Xuantong Zhou, Daisuke Izumi, Mitsuro Kanda, et al "A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study." <i>Molecular Cancer</i> 21, 1. (2022): 44. http://hdl.handle.net/11427/36311en_ZA
dc.identifier.citationMiyoshi, J., Zhu, Z., Luo, A., Toden, S., Zhou, X., Izumi, D., Kanda, M. & Takayama, T. et al. 2022. A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. <i>Molecular Cancer.</i> 21(1):44. http://hdl.handle.net/11427/36311en_ZA
dc.identifier.ris TY - Journal Article AU - Miyoshi, Jinsei AU - Zhu, Zhongxu AU - Luo, Aiping AU - Toden, Shusuke AU - Zhou, Xuantong AU - Izumi, Daisuke AU - Kanda, Mitsuro AU - Takayama, Tetsuji AU - Parker, Iqbal M AU - Wang, Minjie AU - Gao, Feng AU - Zaidi, Ali H AU - Baba, Hideo AU - Kodera, Yasuhiro AU - Cui, Yongping AU - Wang, Xin AU - Liu, Zhihua AU - Goel, Ajay AB - Background Currently, there is no clinically relevant non-invasive biomarker for early detection of esophageal squamous cell carcinoma (ESCC). Herein, we established and evaluated a circulating microRNA (miRNA)-based signature for the early detection of ESCC using a systematic genome-wide miRNA expression profiling analysis. Methods We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n = 108, 238, and 216) and the candidate miRNAs were confirmed in tissue specimens (n = 64) by qRT-PCR. Using a serum training cohort (n = 408), we conducted multivariate logistic regression analysis to develop an ESCC circulating miRNA signature and the signature was subsequently validated in two independent retrospective and two prospective cohorts. Results We identified eighteen initial miRNA candidates from three miRNA expression datasets (n = 108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confirmed the overexpression of 8 miRNAs (miR-103, miR-106b, miR-151, miR-17, miR-181a, miR-21, miR-25, and miR-93) in serum specimens. Using a serum training cohort, we developed a circulating miRNA signature (AUC:0.83 [95%CI:0.79–0.87]) and the diagnostic performance of the miRNA signature was confirmed in two independent validation cohorts (n = 126, AUC:0.80 [95%CI:0.69–0.91]; and n = 165, AUC:0.89 [95%CI:0.83–0.94]). Finally, we demonstrated the diagnostic performance of the 8-miRNA signature in two prospective cohorts (n = 185, AUC:0.92, [95%CI:0.87–0.96]); and (n = 188, AUC:0.93, [95%CI:0.88–0.97]). Importantly, the 8-miRNA signature was superior to current clinical serological markers in discriminating early stage ESCC patients from healthy controls (p < 0.001). Conclusions We have developed a novel and robust circulating miRNA-based signature for early detection of ESCC, which was successfully validated in multiple retrospective and prospective multinational, multicenter cohorts. DA - 2022-02-11 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Molecular Cancer KW - Cancer KW - Liquid biopsy KW - Biomarker KW - Esophageal squamous cell carcinoma KW - microRNA LK - https://open.uct.ac.za PY - 2022 T1 - A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study TI - A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study UR - http://hdl.handle.net/11427/36311 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12943-022-01507-x
dc.identifier.urihttp://hdl.handle.net/11427/36311
dc.identifier.vancouvercitationMiyoshi J, Zhu Z, Luo A, Toden S, Zhou X, Izumi D, et al. A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. Molecular Cancer. 2022;21(1):44. http://hdl.handle.net/11427/36311.en_ZA
dc.language.isoenen_US
dc.language.rfc3066en
dc.publisher.departmentInstitute of Infectious Disease and Molecular Medicineen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceMolecular Canceren_US
dc.source.journalissue1en_US
dc.source.journalvolume21en_US
dc.source.pagination44en_US
dc.source.urihttps://molecular-cancer.biomedcentral.com/
dc.subjectCanceren_US
dc.subjectLiquid biopsyen_US
dc.subjectBiomarkeren_US
dc.subjectEsophageal squamous cell carcinomaen_US
dc.subjectmicroRNAen_US
dc.titleA microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter studyen_US
dc.typeJournal Articleen_US
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