A novel combination of serum microRNAs for the detection of early gastric cancer

Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospi...

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Veröffentlicht in:Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 2021-07, Vol.24 (4), p.835-843
Hauptverfasser: Abe, Seiichiro, Matsuzaki, Juntaro, Sudo, Kazuki, Oda, Ichiro, Katai, Hitoshi, Kato, Ken, Takizawa, Satoko, Sakamoto, Hiromi, Takeshita, Fumitaka, Niida, Shumpei, Saito, Yutaka, Ochiya, Takahiro
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container_issue 4
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container_title Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
container_volume 24
creator Abe, Seiichiro
Matsuzaki, Juntaro
Sudo, Kazuki
Oda, Ichiro
Katai, Hitoshi
Kato, Ken
Takizawa, Satoko
Sakamoto, Hiromi
Takeshita, Fumitaka
Niida, Shumpei
Saito, Yutaka
Ochiya, Takahiro
description Background The aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort. Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene ® ) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.
doi_str_mv 10.1007/s10120-021-01161-0
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Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene ® ) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.</description><identifier>ISSN: 1436-3291</identifier><identifier>EISSN: 1436-3305</identifier><identifier>DOI: 10.1007/s10120-021-01161-0</identifier><identifier>PMID: 33743111</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Abdominal Surgery ; Adult ; Aged ; Aged, 80 and over ; Area Under Curve ; Biomarkers, Tumor - genetics ; Cancer Research ; Case-Control Studies ; Early Detection of Cancer - methods ; Female ; Gastric cancer ; Gastroenterology ; Humans ; Male ; Medicine ; Medicine &amp; Public Health ; MicroRNAs ; MicroRNAs - blood ; Middle Aged ; miRNA ; Nucleotide sequence ; Oligonucleotide Array Sequence Analysis ; Oncology ; Original ; Original Article ; Reproducibility of Results ; Retrospective Studies ; ROC Curve ; Sequence Analysis, RNA - statistics &amp; numerical data ; Stomach Neoplasms - diagnosis ; Surgical Oncology ; Young Adult</subject><ispartof>Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021-07, Vol.24 (4), p.835-843</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. 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Methods This retrospective case–control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene ® ) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set. Results The discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953. Conclusions A novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>33743111</pmid><doi>10.1007/s10120-021-01161-0</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Abdominal Surgery
Adult
Aged
Aged, 80 and over
Area Under Curve
Biomarkers, Tumor - genetics
Cancer Research
Case-Control Studies
Early Detection of Cancer - methods
Female
Gastric cancer
Gastroenterology
Humans
Male
Medicine
Medicine & Public Health
MicroRNAs
MicroRNAs - blood
Middle Aged
miRNA
Nucleotide sequence
Oligonucleotide Array Sequence Analysis
Oncology
Original
Original Article
Reproducibility of Results
Retrospective Studies
ROC Curve
Sequence Analysis, RNA - statistics & numerical data
Stomach Neoplasms - diagnosis
Surgical Oncology
Young Adult
title A novel combination of serum microRNAs for the detection of early gastric cancer
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