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

Jinsei Miyoshi; Zhongxu Zhu; Aiping Luo; Shusuke Toden; Xuantong Zhou; Daisuke Izumi; Mitsuro Kanda; Tetsuji Takayama; Iqbal M. Parker; Minjie Wang; Feng Gao; Ali H. Zaidi; Hideo Baba; Yasuhiro Kodera; Yongping Cui; Xin Wang; Zhihua Liu; Ajay Goel

doi:10.1186/s12943-022-01507-x

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

Jinsei Miyoshi (Co-first Author)
, Zhongxu Zhu (Co-first Author)
, Aiping Luo (Co-first Author)
, Shusuke Toden (Co-first Author)
, Xuantong Zhou
, Daisuke Izumi
, Mitsuro Kanda
, Tetsuji Takayama
, Iqbal M. Parker
, Minjie Wang
, Feng Gao
, Ali H. Zaidi
, Hideo Baba
, Yasuhiro Kodera
, Yongping Cui
, Xin Wang^* (Co-first Author)
, Zhihua Liu^* (Co-first Author)
, Ajay Goel^* (Co-first Author)

^*Corresponding author for this work

Department of Biomedical Sciences

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

84 Citations (Scopus)

106 Downloads (CityUHK Scholars)

Abstract

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 profling analysis.

Methods: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n =108, 238, and 216) and the candidate miRNAs were confrmed 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 identifed eighteen initial miRNA candidates from three miRNA expression datasets (n =108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confrmed 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 confrmed 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.

Original language	English
Article number	44
Journal	Molecular Cancer
Volume	21
Online published	11 Feb 2022
DOIs	https://doi.org/10.1186/s12943-022-01507-x
Publication status	Published - 2022

Funding

The present work was supported by CA72851, CA181572, CA184792, CA187956, and CA202797 grants from the National Cancer Institute, National Institutes of Health, RP140784 from the Cancer Prevention Research Institute of Texas, grants from the Sammons Cancer Center and Baylor Foundation, as well as funds from the Baylor Scott & White Research Institute, Dallas, TX, USA awarded to AG; by grants from the Research Grants Council of the Hong Kong Special Administrative Region, China (Project No. 11103718, 11103619, 11103921, R4017–18, C4041-17GF, AoE/M-401/20), a grant from Guangdong Basic and Applied Basic Research Foundation (Project No. 2019B030302012), and a grant from National Natural Science Foundation of China (Project No. 81802384) awarded to Xin Wang; and by the CMAS Initiative for Innovative Medicine (2021-1-I2M-018) and the National Key R&D Program of China (2021YFC2501000) awarded to Zhihua Liu.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Keywords

Cancer
Liquid biopsy
Biomarker
Esophageal squamous cell carcinoma
microRNA

Publisher's Copyright Statement

This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

RGC Funding Information

RGC-funded

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10.1186/s12943-022-01507-x

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Miyoshi, J., Zhu, Z., Luo, A., Toden, S., Zhou, X., Izumi, D., Kanda, M., Takayama, T., Parker, I. M., Wang, M., Gao, F., Zaidi, A. H., Baba, H., Kodera, Y., Cui, Y., Wang, X., Liu, Z., & Goel, A. (2022). A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. Molecular Cancer, 21, Article 44. https://doi.org/10.1186/s12943-022-01507-x

@article{f8fe1ef3dd65481eb8e708d9603f9074,

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

abstract = "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 profling analysis. Methods: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n =108, 238, and 216) and the candidate miRNAs were confrmed 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 identifed eighteen initial miRNA candidates from three miRNA expression datasets (n =108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confrmed 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 confrmed 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.",

keywords = "Cancer, Liquid biopsy, Biomarker, Esophageal squamous cell carcinoma, microRNA",

author = "Jinsei Miyoshi and Zhongxu Zhu and Aiping Luo and Shusuke Toden and Xuantong Zhou and Daisuke Izumi and Mitsuro Kanda and Tetsuji Takayama and Parker, \{Iqbal M.\} and Minjie Wang and Feng Gao and Zaidi, \{Ali H.\} and Hideo Baba and Yasuhiro Kodera and Yongping Cui and Xin Wang and Zhihua Liu and Ajay Goel",

year = "2022",

doi = "10.1186/s12943-022-01507-x",

language = "English",

volume = "21",

journal = "Molecular Cancer",

issn = "1476-4598",

publisher = "BioMed Central Ltd.",

}

Miyoshi, J, Zhu, Z, Luo, A, Toden, S, Zhou, X, Izumi, D, Kanda, M, Takayama, T, Parker, IM, Wang, M, Gao, F, Zaidi, AH, Baba, H, Kodera, Y, Cui, Y, Wang, X, Liu, Z & Goel, A 2022, 'A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study', Molecular Cancer, vol. 21, 44. https://doi.org/10.1186/s12943-022-01507-x

A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma: a retrospective, prospective and multicenter study. / Miyoshi, Jinsei (Co-first Author); Zhu, Zhongxu (Co-first Author); Luo, Aiping (Co-first Author) et al.
In: Molecular Cancer, Vol. 21, 44, 2022.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - A microRNA-based liquid biopsy signature for the early detection of esophageal squamous cell carcinoma

T2 - a retrospective, prospective and multicenter study

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

PY - 2022

Y1 - 2022

N2 - 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 profling analysis. Methods: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n =108, 238, and 216) and the candidate miRNAs were confrmed 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 identifed eighteen initial miRNA candidates from three miRNA expression datasets (n =108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confrmed 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 confrmed 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.

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 profling analysis. Methods: We performed miRNA candidate discovery using three ESCC tissue miRNA datasets (n =108, 238, and 216) and the candidate miRNAs were confrmed 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 identifed eighteen initial miRNA candidates from three miRNA expression datasets (n =108, 238, and 216) and subsequently validated their expression in ESCC tissues. We thereafter confrmed 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 confrmed 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.

KW - Cancer

KW - Liquid biopsy

KW - Biomarker

KW - Esophageal squamous cell carcinoma

KW - microRNA

UR - https://www.scopus.com/pages/publications/85124576620

UR - https://www.scopus.com/pages/publications/85124576620#tab=impact

U2 - 10.1186/s12943-022-01507-x

DO - 10.1186/s12943-022-01507-x

M3 - RGC 21 - Publication in refereed journal

C2 - 35148754

SN - 1476-4598

VL - 21

JO - Molecular Cancer

JF - Molecular Cancer

M1 - 44

ER -

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

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

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GRF: Overcoming the Intratumor Heterogeneity By Multi-Scale Spatial Characterizations of Tumor Microenvironment for Integrative Colorectal Cancer Classification

AoE(UGC)-ExtU-Lead: Centre for Medical Engineering of Molecular and Biological Probes

GRF: Dissecting Age-dependent Molecular Heterogeneity of Colorectal Cancer and Establishing a Probabilistic Model for Robust Prediction of High-risk Young-onset Colorectal Cancer Patients

Cite this

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

Abstract

Funding

UN SDGs

Research Keywords

Publisher's Copyright Statement

RGC Funding Information

Access Output

Other Access Options

Permanent Link

Other Files and Links

Fingerprint

Projects

GRF: Overcoming the Intratumor Heterogeneity By Multi-Scale Spatial Characterizations of Tumor Microenvironment for Integrative Colorectal Cancer Classification

AoE(UGC)-ExtU-Lead: Centre for Medical Engineering of Molecular and Biological Probes

GRF: Dissecting Age-dependent Molecular Heterogeneity of Colorectal Cancer and Establishing a Probabilistic Model for Robust Prediction of High-risk Young-onset Colorectal Cancer Patients

Cite this