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 |
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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 < 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.</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 & 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 & 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 < 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.</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 & Wilkins</general><general>Copyright Wolters Kluwer Health, Inc. All rights reserved</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20210301</creationdate><title>Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4529-13d6fd110c9ecb84f68daaec3b0192e1658a9379ce5f5f7e7600ba370c1e16443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Biomarkers, Tumor - genetics</topic><topic>China</topic><topic>Esophageal Squamous Cell Carcinoma - genetics</topic><topic>Esophageal Squamous Cell Carcinoma - pathology</topic><topic>Esophageal Squamous Cell Carcinoma - surgery</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Humans</topic><topic>Lymphatic Metastasis</topic><topic>Male</topic><topic>Microarray Analysis</topic><topic>MicroRNAs - genetics</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>Prognosis</topic><topic>Retrospective Studies</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><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><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wen, Jing</au><au>Wang, Geng</au><au>Xie, Xuan</au><au>Lin, Guangrong</au><au>Yang, Hong</au><au>Luo, Kongjia</au><au>Liu, Qianwen</au><au>Ling, Yihong</au><au>Xie, Xiuying</au><au>Lin, Peng</au><au>Chen, Yuping</au><au>Zhang, Huizhong</au><au>Rong, Tiehua</au><au>Fu, Jianhua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic Value of a Four-miRNA Signature in Patients With Lymph Node Positive Locoregional Esophageal Squamous Cell Carcinoma Undergoing Complete Surgical Resection</atitle><jtitle>Annals of surgery</jtitle><addtitle>Ann Surg</addtitle><date>2021-03-01</date><risdate>2021</risdate><volume>273</volume><issue>3</issue><spage>523</spage><epage>531</epage><pages>523-531</pages><issn>0003-4932</issn><eissn>1528-1140</eissn><abstract>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.</abstract><cop>United States</cop><pub>Lippincott Williams & 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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