Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection

OBJECTIVE:This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA:Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are...

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Veröffentlicht in:Annals of surgery 2021-03, Vol.273 (3), p.523-531
Hauptverfasser: Wen, Jing, Wang, Geng, Xie, Xuan, Lin, Guangrong, Yang, Hong, Luo, Kongjia, Liu, Qianwen, Ling, Yihong, Xie, Xiuying, Lin, Peng, Chen, Yuping, Zhang, Huizhong, Rong, Tiehua, Fu, Jianhua
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container_end_page 531
container_issue 3
container_start_page 523
container_title Annals of surgery
container_volume 273
creator Wen, Jing
Wang, Geng
Xie, Xuan
Lin, Guangrong
Yang, Hong
Luo, Kongjia
Liu, Qianwen
Ling, Yihong
Xie, Xiuying
Lin, Peng
Chen, Yuping
Zhang, Huizhong
Rong, Tiehua
Fu, Jianhua
description OBJECTIVE:This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA:Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS:ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS:Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI)0–20.3] than those with low-risk scores (50.3%, 95% CI40.0–60.7; P < 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P < 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION:Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.
doi_str_mv 10.1097/SLA.0000000000003369
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SUMMARY OF BACKGROUND DATA:Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS:ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS:Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI)0–20.3] than those with low-risk scores (50.3%, 95% CI40.0–60.7; P &lt; 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P &lt; 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION:Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.</description><identifier>ISSN: 0003-4932</identifier><identifier>EISSN: 1528-1140</identifier><identifier>DOI: 10.1097/SLA.0000000000003369</identifier><identifier>PMID: 31058700</identifier><language>eng</language><publisher>United States: Lippincott Williams &amp; Wilkins</publisher><subject>Aged ; Biomarkers, Tumor - genetics ; China ; Esophageal Squamous Cell Carcinoma - genetics ; Esophageal Squamous Cell Carcinoma - pathology ; Esophageal Squamous Cell Carcinoma - surgery ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphatic Metastasis ; Male ; Microarray Analysis ; MicroRNAs - genetics ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies</subject><ispartof>Annals of surgery, 2021-03, Vol.273 (3), p.523-531</ispartof><rights>Lippincott Williams &amp; Wilkins</rights><rights>Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4529-13d6fd110c9ecb84f68daaec3b0192e1658a9379ce5f5f7e7600ba370c1e16443</citedby><cites>FETCH-LOGICAL-c4529-13d6fd110c9ecb84f68daaec3b0192e1658a9379ce5f5f7e7600ba370c1e16443</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31058700$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wen, Jing</creatorcontrib><creatorcontrib>Wang, Geng</creatorcontrib><creatorcontrib>Xie, Xuan</creatorcontrib><creatorcontrib>Lin, Guangrong</creatorcontrib><creatorcontrib>Yang, Hong</creatorcontrib><creatorcontrib>Luo, Kongjia</creatorcontrib><creatorcontrib>Liu, Qianwen</creatorcontrib><creatorcontrib>Ling, Yihong</creatorcontrib><creatorcontrib>Xie, Xiuying</creatorcontrib><creatorcontrib>Lin, Peng</creatorcontrib><creatorcontrib>Chen, Yuping</creatorcontrib><creatorcontrib>Zhang, Huizhong</creatorcontrib><creatorcontrib>Rong, Tiehua</creatorcontrib><creatorcontrib>Fu, Jianhua</creatorcontrib><title>Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection</title><title>Annals of surgery</title><addtitle>Ann Surg</addtitle><description>OBJECTIVE:This study was intended to identify prognostic biomarkers for lymph node (LN)-positive locoregional esophageal squamous cell carcinoma (ESCC) patients. SUMMARY OF BACKGROUND DATA:Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS:ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS:Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI)0–20.3] than those with low-risk scores (50.3%, 95% CI40.0–60.7; P &lt; 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P &lt; 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION:Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.</description><subject>Aged</subject><subject>Biomarkers, Tumor - genetics</subject><subject>China</subject><subject>Esophageal Squamous Cell Carcinoma - genetics</subject><subject>Esophageal Squamous Cell Carcinoma - pathology</subject><subject>Esophageal Squamous Cell Carcinoma - surgery</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Humans</subject><subject>Lymphatic Metastasis</subject><subject>Male</subject><subject>Microarray Analysis</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>Prognosis</subject><subject>Retrospective Studies</subject><issn>0003-4932</issn><issn>1528-1140</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkctu1DAUhi0EokPhDRDykk3K8SW35ShqASkqow6FZeRxThJDEqe2Q9UX4jlxmYIQC7Bk-fb9v4_OT8hLBmcMyvzNvt6ewR9DiKx8RDYs5UXCmITHZHN_m8hS8BPyzPsvAEwWkD8lJ4JBWuQAG_J952w_Wx-Mpp_UuCK1HVX0wq4umczV5ZbuTT-rsDqkZqY7FQzOwdPPJgy0vpuWgV7aFunOehPMN6S11dZhb-ysRnru7TKoHuN2f7Oqya6eVjiOtFJOm9lOil7PLbremrmnlZ2WEQPS_ep6o6PoCj3qEL2ekyedGj2-eFhPyfXF-cfqXVJ_ePu-2taJlikvEybarGsZA12iPhSyy4pWKdTiAKzkyLK0UKXIS41pl3Y55hnAQYkcNIuPUopT8vrouzh7s6IPzWS8jhWrGWPxDeeCMwGySCMqj6h21nuHXbM4Myl31zBo7hNqYkLN3wlF2auHH9bDhO1v0a9IIlAcgVs7BnT-67jeomuG2MQw_M9b_kP6k4sdSDhwBiIekjg5iB8Pi67j</recordid><startdate>20210301</startdate><enddate>20210301</enddate><creator>Wen, Jing</creator><creator>Wang, Geng</creator><creator>Xie, Xuan</creator><creator>Lin, Guangrong</creator><creator>Yang, Hong</creator><creator>Luo, Kongjia</creator><creator>Liu, Qianwen</creator><creator>Ling, Yihong</creator><creator>Xie, Xiuying</creator><creator>Lin, Peng</creator><creator>Chen, Yuping</creator><creator>Zhang, Huizhong</creator><creator>Rong, Tiehua</creator><creator>Fu, Jianhua</creator><general>Lippincott Williams &amp; Wilkins</general><general>Copyright Wolters Kluwer Health, Inc. 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SUMMARY OF BACKGROUND DATA:Surgery is a major treatment for LN-positive locoregional ESCC patients in China. However, patient outcomes are poor and heterogeneous. METHODS:ESCC-associated miRNAs were identified by microarray and validated by quantitative real-time polymerase chain reaction analyses in ESCC and normal esophageal epithelial samples. A multi-miRNA based classifier was established using a least absolute shrinkage and selection operator model in a training set of 145 LN-positive locoregional ESCCs, and further assessed in internal testing and independent validation sets of 145 and 243 patients, respectively. RESULTS:Twenty ESCC-associated miRNAs were identified and validated. A 4-miRNA based classifier (miR-135b-5p, miR-139-5p, miR-29c-5p, and miR-338-3p) was generated to classify LN-positive locoregional ESCC patients into high and low-risk groups. Patients with high-risk scores in the training set had a lower 5-year overall survival rate [8.7%, 95% confidence interval (CI)0–20.3] than those with low-risk scores (50.3%, 95% CI40.0–60.7; P &lt; 0.0001). The prognostic accuracy of the classifier was validated in the internal testing (P &lt; 0.0001) and independent validation sets (P = 0.00073). Multivariate survival analyses showed that the 4-miRNA based classifier was an independent prognostic factor, and the combination of the 4-miRNA based classifier and clinicopathological prognostic factors significantly improved the prognostic accuracy of clinicopathological prognostic factors alone. CONCLUSION:Our 4-miRNA based classifier is a reliable prognostic prediction tool for overall survival in LN-positive locoregional ESCC patients and might offer a novel probability of ESCC treatment individualization.</abstract><cop>United States</cop><pub>Lippincott Williams &amp; Wilkins</pub><pmid>31058700</pmid><doi>10.1097/SLA.0000000000003369</doi><tpages>9</tpages></addata></record>
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subjects Aged
Biomarkers, Tumor - genetics
China
Esophageal Squamous Cell Carcinoma - genetics
Esophageal Squamous Cell Carcinoma - pathology
Esophageal Squamous Cell Carcinoma - surgery
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Lymphatic Metastasis
Male
Microarray Analysis
MicroRNAs - genetics
Middle Aged
Neoplasm Staging
Prognosis
Retrospective Studies
title Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection
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