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

Molecular Cancer

Yongping Cui¹  Shusuke Toden²  Jinsei Miyoshi³  Ajay Goel⁴  Minjie Wang⁵  Daisuke Izumi⁶  Hideo Baba⁶  Yasuhiro Kodera⁷  Mitsuro Kanda⁷  Tetsuji Takayama⁸  Xin Wang⁹  Zhongxu Zhu^1,10  Iqbal M. Parker^1,11  Ali H. Zaidi^1,12  Zhihua Liu^1,13  Aiping Luo^1,13  Xuantong Zhou^1,13  Feng Gao^1,14 

[1] Cancer Institute, Shenzhen Bay Laboratory, Shenzhen, China;Cancer Institute, Peking University Shenzhen Hospital, Shenzhen Peking University-Hong Kong University of Science and technology (PKU-HKUST) Medical Center, Shenzhen, China;Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA;Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA;Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan;Department of Gastroenterology, Kawashima Hospital, Tokushima, Japan;Center for Gastrointestinal Research; Center for Translational Genomics and Oncology, Baylor Scott & White Research Institute and Charles A. Sammons Cancer Center, Baylor University Medical Center, Dallas, TX, USA;Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope, Duarte, CA, USA;City of Hope Comprehensive Cancer Center, Duarte, CA, USA;Department of Clinical Laboratory, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China;Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan;Department of Gastroenterological Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan;Department of Gastroenterology and Oncology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan;Department of Surgery, The Chinese University of Hong Kong. Prince of Wales Hospital, Shatin, N.T., Hong Kong, SAR, China;Department of Surgery, The Chinese University of Hong Kong. Prince of Wales Hospital, Shatin, N.T., Hong Kong, SAR, China;Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, SAR, China;Division of Medical Biochemistry and Structural Biology, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa;Esophageal and Lung Institute, Allegheny Health Network, Pittsburgh, PA, USA;State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100021, Beijing, China;The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China;

关键词: Cancer;    Liquid biopsy;    Biomarker;    Esophageal squamous cell carcinoma;    microRNA;   

DOI  :  10.1186/s12943-022-01507-x

来源: Springer

【 摘 要 】

BackgroundCurrently, 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.MethodsWe 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.ResultsWe 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).ConclusionsWe 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.

【 授权许可】

CC BY