Xin Guo , Yunhua Peng , Qiying Song , Jiangpeng Wei , Xinxin Wang , Yi Ru , Shenhui Xu , Xin Cheng , Xiaohua Li , Di Wu , Lubin Chen , Bo Wei , Xiaohui Lv , Gang Ji
{"title":"早期检测癌症患者的液体活检特征。","authors":"Xin Guo , Yunhua Peng , Qiying Song , Jiangpeng Wei , Xinxin Wang , Yi Ru , Shenhui Xu , Xin Cheng , Xiaohua Li , Di Wu , Lubin Chen , Bo Wei , Xiaohui Lv , Gang Ji","doi":"10.1053/j.gastro.2023.02.044","DOIUrl":null,"url":null,"abstract":"<div><h3>Background & Aims</h3><p>Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC.</p></div><div><h3>Methods</h3><p><span>The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis<span>, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using </span></span>transcriptomic profiling in discovery phase. The extracellular vesicle (EV)–derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69).</p></div><div><h3>Results</h3><p><span>In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073–0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi’an cohort, AUC: 0.8839; 95% CI: 0.8336–0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597–0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other </span>gastrointestinal tumor plasma samples indicated its GC specificity.</p></div><div><h3>Conclusions</h3><p>EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.</p></div>","PeriodicalId":12590,"journal":{"name":"Gastroenterology","volume":"165 2","pages":"Pages 402-413.e13"},"PeriodicalIF":25.7000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients\",\"authors\":\"Xin Guo , Yunhua Peng , Qiying Song , Jiangpeng Wei , Xinxin Wang , Yi Ru , Shenhui Xu , Xin Cheng , Xiaohua Li , Di Wu , Lubin Chen , Bo Wei , Xiaohui Lv , Gang Ji\",\"doi\":\"10.1053/j.gastro.2023.02.044\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background & Aims</h3><p>Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC.</p></div><div><h3>Methods</h3><p><span>The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis<span>, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using </span></span>transcriptomic profiling in discovery phase. The extracellular vesicle (EV)–derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69).</p></div><div><h3>Results</h3><p><span>In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073–0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi’an cohort, AUC: 0.8839; 95% CI: 0.8336–0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597–0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other </span>gastrointestinal tumor plasma samples indicated its GC specificity.</p></div><div><h3>Conclusions</h3><p>EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.</p></div>\",\"PeriodicalId\":12590,\"journal\":{\"name\":\"Gastroenterology\",\"volume\":\"165 2\",\"pages\":\"Pages 402-413.e13\"},\"PeriodicalIF\":25.7000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gastroenterology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0016508523002366\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0016508523002366","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
A Liquid Biopsy Signature for the Early Detection of Gastric Cancer in Patients
Background & Aims
Diagnosing gastric cancer (GC) while the disease remains eligible for surgical resection is challenging. In view of this clinical challenge, novel and robust biomarkers for early detection thus improving prognosis of GC are necessary. The present study is to develop a blood-based long noncoding RNA (LR) signature for the early-detection of GC.
Methods
The present 3-step study incorporated data from 2141 patients, including 888 with GC, 158 with chronic atrophic gastritis, 193 with intestinal metaplasia, 501 healthy donors, and 401 with other gastrointestinal cancers. The LR profile of stage I GC tissue samples were analyzed using transcriptomic profiling in discovery phase. The extracellular vesicle (EV)–derived LR signature was identified with a training cohort (n = 554) and validated with 2 external cohorts (n = 429 and n = 504) and a supplemental cohort (n = 69).
Results
In discovery phase, one LR (GClnc1) was found to be up-regulated in both tissue and circulating EV samples with an area under the curve (AUC) of 0.9369 (95% confidence interval [CI], 0.9073–0.9664) for early-stage GC (stage I/II). The diagnostic performance of this biomarker was further confirmed in 2 external validation cohorts (Xi’an cohort, AUC: 0.8839; 95% CI: 0.8336–0.9342; Beijing cohort, AUC: 0.9018; 95% CI: 0.8597–0.9439). Moreover, EV-derived GClnc1 robustly distinguished early-stage GC from precancerous lesions (chronic atrophic gastritis and intestinal metaplasia) and GC with negative traditional gastrointestinal biomarkers (CEA, CA72-4, and CA19-9). The low levels of this biomarker in postsurgery and other gastrointestinal tumor plasma samples indicated its GC specificity.
Conclusions
EV-derived GClnc1 serves as a circulating biomarker for the early detection of GC, thus providing opportunities for curative surgery and improved survival outcomes.
期刊介绍:
Gastroenterology is the most prominent journal in the field of gastrointestinal disease. It is the flagship journal of the American Gastroenterological Association and delivers authoritative coverage of clinical, translational, and basic studies of all aspects of the digestive system, including the liver and pancreas, as well as nutrition.
Some regular features of Gastroenterology include original research studies by leading authorities, comprehensive reviews and perspectives on important topics in adult and pediatric gastroenterology and hepatology. The journal also includes features such as editorials, correspondence, and commentaries, as well as special sections like "Mentoring, Education and Training Corner," "Diversity, Equity and Inclusion in GI," "Gastro Digest," "Gastro Curbside Consult," and "Gastro Grand Rounds."
Gastroenterology also provides digital media materials such as videos and "GI Rapid Reel" animations. It is abstracted and indexed in various databases including Scopus, Biological Abstracts, Current Contents, Embase, Nutrition Abstracts, Chemical Abstracts, Current Awareness in Biological Sciences, PubMed/Medline, and the Science Citation Index.