Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling

Kazuki Sudo, Ken Kato, Juntaro Matsuzaki, Narikazu Boku, Seiichiro Abe, Yutaka Saito, Hiroyuki Daiko, Satoko Takizawa, Yoshiaki Aoki, Hiromi Sakamoto, Shumpei Niida, Fumitaka Takeshita, Takahiro Fukuda, Takahiro Ochiya

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. Design, Setting, and Participants: In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. Main Outcomes and Measures: The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. Results: In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4% male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1% male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0% male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7% male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. Conclusions and Relevance: What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.

Original languageEnglish
Pages (from-to)e194573
JournalJAMA network open
Volume2
Issue number5
DOIs
Publication statusPublished - 2019 May 3
Externally publishedYes

Fingerprint

MicroRNAs
ROC Curve
Serum
Geriatrics
Esophageal Squamous Cell Carcinoma
Cancer Care Facilities
Sensitivity and Specificity
Neoplasms
Tokyo
Discriminant Analysis
Esophageal Neoplasms
Multicenter Studies
Case-Control Studies
Japan
Outcome Assessment (Health Care)
Prospective Studies
Mortality
Health
Population

Cite this

Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling. / Sudo, Kazuki; Kato, Ken; Matsuzaki, Juntaro; Boku, Narikazu; Abe, Seiichiro; Saito, Yutaka; Daiko, Hiroyuki; Takizawa, Satoko; Aoki, Yoshiaki; Sakamoto, Hiromi; Niida, Shumpei; Takeshita, Fumitaka; Fukuda, Takahiro; Ochiya, Takahiro.

In: JAMA network open, Vol. 2, No. 5, 03.05.2019, p. e194573.

Research output: Contribution to journalArticle

Sudo, K, Kato, K, Matsuzaki, J, Boku, N, Abe, S, Saito, Y, Daiko, H, Takizawa, S, Aoki, Y, Sakamoto, H, Niida, S, Takeshita, F, Fukuda, T & Ochiya, T 2019, 'Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling', JAMA network open, vol. 2, no. 5, pp. e194573. https://doi.org/10.1001/jamanetworkopen.2019.4573
Sudo, Kazuki ; Kato, Ken ; Matsuzaki, Juntaro ; Boku, Narikazu ; Abe, Seiichiro ; Saito, Yutaka ; Daiko, Hiroyuki ; Takizawa, Satoko ; Aoki, Yoshiaki ; Sakamoto, Hiromi ; Niida, Shumpei ; Takeshita, Fumitaka ; Fukuda, Takahiro ; Ochiya, Takahiro. / Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling. In: JAMA network open. 2019 ; Vol. 2, No. 5. pp. e194573.
@article{55a041cfd03e47cdbd8bc81c66c4f8eb,
title = "Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling",
abstract = "Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. Design, Setting, and Participants: In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. Main Outcomes and Measures: The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. Results: In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4{\%} male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1{\%} male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0{\%} male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7{\%} male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. Conclusions and Relevance: What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.",
author = "Kazuki Sudo and Ken Kato and Juntaro Matsuzaki and Narikazu Boku and Seiichiro Abe and Yutaka Saito and Hiroyuki Daiko and Satoko Takizawa and Yoshiaki Aoki and Hiromi Sakamoto and Shumpei Niida and Fumitaka Takeshita and Takahiro Fukuda and Takahiro Ochiya",
year = "2019",
month = "5",
day = "3",
doi = "10.1001/jamanetworkopen.2019.4573",
language = "English",
volume = "2",
pages = "e194573",
journal = "JAMA network open",
issn = "2574-3805",
publisher = "American Medical Association",
number = "5",

}

TY - JOUR

T1 - Development and Validation of an Esophageal Squamous Cell Carcinoma Detection Model by Large-Scale MicroRNA Profiling

AU - Sudo, Kazuki

AU - Kato, Ken

AU - Matsuzaki, Juntaro

AU - Boku, Narikazu

AU - Abe, Seiichiro

AU - Saito, Yutaka

AU - Daiko, Hiroyuki

AU - Takizawa, Satoko

AU - Aoki, Yoshiaki

AU - Sakamoto, Hiromi

AU - Niida, Shumpei

AU - Takeshita, Fumitaka

AU - Fukuda, Takahiro

AU - Ochiya, Takahiro

PY - 2019/5/3

Y1 - 2019/5/3

N2 - Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. Design, Setting, and Participants: In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. Main Outcomes and Measures: The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. Results: In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4% male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1% male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0% male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7% male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. Conclusions and Relevance: What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.

AB - Importance: Patients with late-stage esophageal squamous cell carcinoma (ESCC) have a poor prognosis. Noninvasive screening tests using serum microRNAs (miRNAs) to accurately detect early-stage ESCC are needed to improve mortality. Objective: To establish a model using serum miRNAs to distinguish patients with ESCC from noncancer controls. Design, Setting, and Participants: In this case-control study, serum miRNA expression profiles of patients with ESCC (n = 566) and control patients without cancer (n = 4965) were retrospectively analyzed to establish a diagnostic model, which was tested in a training set and confirmed in a validation set. Patients histologically diagnosed as having ESCC who did not receive prior therapy or have a past or concurrent cancer other than ESCC were enrolled from the National Cancer Center Hospital in Tokyo, Japan. Between October 2010 and November 2015, control samples were collected from the National Cancer Center Biobank, the Biobank of the National Center for Geriatrics and Gerontology, and the general population undergoing routine health examination. Data analysis was performed between August 2015 and October 2018. Serum samples were randomly divided into discovery and validation sets. Main Outcomes and Measures: The expression of 2565 miRNAs was assessed in each sample. The discriminant model (named the EC index) was evaluated in the training set using Fisher linear discriminant analysis with a greedy algorithm. Receiver operating characteristic curve analysis evaluated the diagnostic ability of the model in the validation set. Results: In the training set, 283 patients with esophageal cancer (median age, 67 years [range, 37-90 years]; 83.4% male) were compared with 283 control patients (median age, 54 years [range, 22-100 years]; 43.1% male), and the EC index was constructed using 6 miRNAs (miR-8073, miR-6820-5p, miR-6794-5p, miR-3196, miR-744-5p, and miR-6799-5p). The area under the receiver operating characteristic curve was 1.00, with sensitivity of 1.00 and specificity of 0.98. The validation set included 283 patients (median age, 66 years [range, 42-87 years]; 83.0% male) and 4682 control patients (median age, 68 years [range, 20-98 years]; 44.7% male), and the area under the receiver operating characteristic curve for the EC index was 1.00, with sensitivity of 0.96 and specificity of 0.98. Conclusions and Relevance: What appears to be novel serum miRNA discriminant model was developed for the diagnosis of ESCC. A multicenter prospective study is ongoing to confirm the present observations.

UR - http://www.scopus.com/inward/record.url?scp=85066843258&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066843258&partnerID=8YFLogxK

U2 - 10.1001/jamanetworkopen.2019.4573

DO - 10.1001/jamanetworkopen.2019.4573

M3 - Article

C2 - 31125107

AN - SCOPUS:85066843258

VL - 2

SP - e194573

JO - JAMA network open

JF - JAMA network open

SN - 2574-3805

IS - 5

ER -