Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer
Objectives Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell‐free DNA from preoperative peritoneal lavage fluid (PPLF) and perip...
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| creator | Hu, Xuan‐Yu Ling, Zhe‐Nan Hong, Lian‐Lian Yu, Qi‐Ming Li, Pei Ling, Zhi‐Qiang |
| description | Objectives
Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell‐free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients.
Methods
The status of THBS1 methylation was detected by quantitative methylation‐specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve.
Results
Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p |
| doi_str_mv | 10.1002/jcla.23936 |
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Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell‐free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients.
Methods
The status of THBS1 methylation was detected by quantitative methylation‐specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve.
Results
Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non‐atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001).
Conclusion
Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients.
Postoperative recurrence of gastric cancer usually occurs in the peritoneum, and peritoneal dissemination and recurrence are the main causes of poor prognosis. Therefore, it is very necessary to find a biomarker that can predict peritoneal dissemination of gastric cancer cells. Here, we found that THBS1 methylation levels in preoperative serum or peritoneal fluid can accurately predict peritoneal dissemination and suggest a poor prognosis in patients with gastric cancer.</description><identifier>ISSN: 0887-8013</identifier><identifier>EISSN: 1098-2825</identifier><identifier>DOI: 10.1002/jcla.23936</identifier><identifier>PMID: 34390026</identifier><language>eng</language><publisher>United States: John Wiley & Sons, Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Angiogenesis ; Antigens ; Ascitic Fluid - metabolism ; Ascitic Fluid - pathology ; Biomarkers ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - genetics ; Biopsy ; Case-Control Studies ; Cellular biology ; Circulating Tumor DNA - blood ; Circulating Tumor DNA - genetics ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Female ; Follow-Up Studies ; Gastric cancer ; gastric carcinoma ; Gastritis ; Genetic testing ; Hospitals ; Humans ; Male ; Medical prognosis ; Medical research ; Metastases ; Metastasis ; methylation ; Middle Aged ; Peripheral blood ; peritoneal dissemination ; Peritoneal Neoplasms - blood ; Peritoneal Neoplasms - genetics ; Peritoneal Neoplasms - secondary ; Peritoneal Neoplasms - surgery ; Peritoneum ; Prognosis ; Stomach Neoplasms - blood ; Stomach Neoplasms - genetics ; Stomach Neoplasms - pathology ; Stomach Neoplasms - surgery ; Survival analysis ; Survival Rate ; THBS1 gene ; Thrombospondin ; Thrombospondin 1 - blood ; Thrombospondin 1 - genetics ; Tumorigenesis</subject><ispartof>Journal of clinical laboratory analysis, 2021-09, Vol.35 (9), p.e23936-n/a</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC</rights><rights>2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4486-f4225ddd569ba5af1df984062d388681606db4dc199f133463cf2abcb97fe5a33</citedby><cites>FETCH-LOGICAL-c4486-f4225ddd569ba5af1df984062d388681606db4dc199f133463cf2abcb97fe5a33</cites><orcidid>0000-0003-2155-1111</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418496/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8418496/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34390026$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hu, Xuan‐Yu</creatorcontrib><creatorcontrib>Ling, Zhe‐Nan</creatorcontrib><creatorcontrib>Hong, Lian‐Lian</creatorcontrib><creatorcontrib>Yu, Qi‐Ming</creatorcontrib><creatorcontrib>Li, Pei</creatorcontrib><creatorcontrib>Ling, Zhi‐Qiang</creatorcontrib><title>Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer</title><title>Journal of clinical laboratory analysis</title><addtitle>J Clin Lab Anal</addtitle><description>Objectives
Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell‐free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients.
Methods
The status of THBS1 methylation was detected by quantitative methylation‐specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve.
Results
Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non‐atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001).
Conclusion
Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients.
Postoperative recurrence of gastric cancer usually occurs in the peritoneum, and peritoneal dissemination and recurrence are the main causes of poor prognosis. Therefore, it is very necessary to find a biomarker that can predict peritoneal dissemination of gastric cancer cells. Here, we found that THBS1 methylation levels in preoperative serum or peritoneal fluid can accurately predict peritoneal dissemination and suggest a poor prognosis in patients with gastric cancer.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Angiogenesis</subject><subject>Antigens</subject><subject>Ascitic Fluid - metabolism</subject><subject>Ascitic Fluid - pathology</subject><subject>Biomarkers</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Biopsy</subject><subject>Case-Control Studies</subject><subject>Cellular biology</subject><subject>Circulating Tumor DNA - blood</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Gastric cancer</subject><subject>gastric carcinoma</subject><subject>Gastritis</subject><subject>Genetic testing</subject><subject>Hospitals</subject><subject>Humans</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>methylation</subject><subject>Middle Aged</subject><subject>Peripheral blood</subject><subject>peritoneal dissemination</subject><subject>Peritoneal Neoplasms - blood</subject><subject>Peritoneal Neoplasms - genetics</subject><subject>Peritoneal Neoplasms - secondary</subject><subject>Peritoneal Neoplasms - surgery</subject><subject>Peritoneum</subject><subject>Prognosis</subject><subject>Stomach Neoplasms - blood</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - pathology</subject><subject>Stomach Neoplasms - surgery</subject><subject>Survival analysis</subject><subject>Survival Rate</subject><subject>THBS1 gene</subject><subject>Thrombospondin</subject><subject>Thrombospondin 1 - blood</subject><subject>Thrombospondin 1 - genetics</subject><subject>Tumorigenesis</subject><issn>0887-8013</issn><issn>1098-2825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kV1rFDEUhoModlu98QdIwBsRpuZrssmNsF0_qix6Yb0OmSSzzTaTbJOZyv77Zru1WC-EAzmQ5zycwwvAK4xOMULk_cYEfUqopPwJmGEkRUMEaZ-CGRJi3giE6RE4LmWDEBIS8-fgiDIq6ySfgWHps5mCHn1cw8GNl7vaOwsvzs9-Yvjx-6JAXQvGdOMCHHS-chn2KcNtdtabu7Gty35M0ekArS_FDT5WX4rQR7jWZczeQKOjcfkFeNbrUNzL-_cE_Pr86WJ53qx-fPm6XKwaw5jgTc8Iaa21LZedbnWPbS8FQ5xYKgQXmCNuO2YNlrLHlDJOTU90Zzo5712rKT0BHw7e7dQNzhoXx6yD2mZfL9ippL16_BP9pVqnGyUYFkzyKnh7L8jpenJlVIMvxoWgo0tTUaTlmAmBmKjom3_QTZpyrOftKYkEnjNUqXcHyuRUSnb9wzIYqX2Kap-iukuxwq__Xv8B_RNbBfAB-O2D2_1Hpb4tV4uD9BbPwqjf</recordid><startdate>202109</startdate><enddate>202109</enddate><creator>Hu, Xuan‐Yu</creator><creator>Ling, Zhe‐Nan</creator><creator>Hong, Lian‐Lian</creator><creator>Yu, Qi‐Ming</creator><creator>Li, Pei</creator><creator>Ling, Zhi‐Qiang</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><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>3V.</scope><scope>7QP</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2155-1111</orcidid></search><sort><creationdate>202109</creationdate><title>Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer</title><author>Hu, Xuan‐Yu ; Ling, Zhe‐Nan ; Hong, Lian‐Lian ; Yu, Qi‐Ming ; Li, Pei ; Ling, Zhi‐Qiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4486-f4225ddd569ba5af1df984062d388681606db4dc199f133463cf2abcb97fe5a33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Angiogenesis</topic><topic>Antigens</topic><topic>Ascitic Fluid - metabolism</topic><topic>Ascitic Fluid - pathology</topic><topic>Biomarkers</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Biopsy</topic><topic>Case-Control Studies</topic><topic>Cellular biology</topic><topic>Circulating Tumor DNA - blood</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Gastric cancer</topic><topic>gastric carcinoma</topic><topic>Gastritis</topic><topic>Genetic testing</topic><topic>Hospitals</topic><topic>Humans</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>methylation</topic><topic>Middle Aged</topic><topic>Peripheral blood</topic><topic>peritoneal dissemination</topic><topic>Peritoneal Neoplasms - blood</topic><topic>Peritoneal Neoplasms - genetics</topic><topic>Peritoneal Neoplasms - secondary</topic><topic>Peritoneal Neoplasms - surgery</topic><topic>Peritoneum</topic><topic>Prognosis</topic><topic>Stomach Neoplasms - blood</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - pathology</topic><topic>Stomach Neoplasms - surgery</topic><topic>Survival analysis</topic><topic>Survival Rate</topic><topic>THBS1 gene</topic><topic>Thrombospondin</topic><topic>Thrombospondin 1 - blood</topic><topic>Thrombospondin 1 - genetics</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hu, Xuan‐Yu</creatorcontrib><creatorcontrib>Ling, Zhe‐Nan</creatorcontrib><creatorcontrib>Hong, Lian‐Lian</creatorcontrib><creatorcontrib>Yu, Qi‐Ming</creatorcontrib><creatorcontrib>Li, Pei</creatorcontrib><creatorcontrib>Ling, Zhi‐Qiang</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical laboratory analysis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hu, Xuan‐Yu</au><au>Ling, Zhe‐Nan</au><au>Hong, Lian‐Lian</au><au>Yu, Qi‐Ming</au><au>Li, Pei</au><au>Ling, Zhi‐Qiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer</atitle><jtitle>Journal of clinical laboratory analysis</jtitle><addtitle>J Clin Lab Anal</addtitle><date>2021-09</date><risdate>2021</risdate><volume>35</volume><issue>9</issue><spage>e23936</spage><epage>n/a</epage><pages>e23936-n/a</pages><issn>0887-8013</issn><eissn>1098-2825</eissn><abstract>Objectives
Thrombospondin 1 (THBS1) is known to play a key role in tumor metastasis, and aberrant DNA methylation is one of the mechanisms regulating THBS1. The present study investigated whether methylated THBS1 in circulating cell‐free DNA from preoperative peritoneal lavage fluid (PPLF) and peripheral blood could be used as a potential biomarker for predicting peritoneal dissemination in gastric cancer (GC) patients.
Methods
The status of THBS1 methylation was detected by quantitative methylation‐specific PCR (MSP) in tumor tissues, paired PPLF, and serum from 92 GC patients. The correlation between methylated THBS1 levels and peritoneal dissemination of GC was studied, and its diagnostic value for predicting peritoneal dissemination was clarified by the receiver operating characteristic (ROC) curve.
Results
Aberrant THBS1 methylation in tumor tissues was significantly higher than that in paracancerous normal tissues (p < 0.0001). No THBS1 methylation was found in 40 healthy controls, and partial methylation was detected in 3 of 48 patients with chronic non‐atrophic gastritis. The frequency of THBS1 methylation in pairing PPLF and serum from 92 GC patients was 52.2% (48/92) and 58.7% (54/92), respectively. The results of methylated THBS1 in pairing PPLF and serum were similar to those of tumor tissues. Aberrant THBS1 methylation in tumor tissues and pairing PPLF or serum was closely related to peritoneal dissemination, tumor progression, and poor prognosis (all p < 0.0001).
Conclusion
Circulating methylated THBS1 DNAs in PPLF/serum may predict peritoneal dissemination, a potential poor prognostic factor for GC patients.
Postoperative recurrence of gastric cancer usually occurs in the peritoneum, and peritoneal dissemination and recurrence are the main causes of poor prognosis. Therefore, it is very necessary to find a biomarker that can predict peritoneal dissemination of gastric cancer cells. Here, we found that THBS1 methylation levels in preoperative serum or peritoneal fluid can accurately predict peritoneal dissemination and suggest a poor prognosis in patients with gastric cancer.</abstract><cop>United States</cop><pub>John Wiley & Sons, Inc</pub><pmid>34390026</pmid><doi>10.1002/jcla.23936</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-2155-1111</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Angiogenesis Antigens Ascitic Fluid - metabolism Ascitic Fluid - pathology Biomarkers Biomarkers, Tumor - blood Biomarkers, Tumor - genetics Biopsy Case-Control Studies Cellular biology Circulating Tumor DNA - blood Circulating Tumor DNA - genetics Deoxyribonucleic acid DNA DNA Methylation Female Follow-Up Studies Gastric cancer gastric carcinoma Gastritis Genetic testing Hospitals Humans Male Medical prognosis Medical research Metastases Metastasis methylation Middle Aged Peripheral blood peritoneal dissemination Peritoneal Neoplasms - blood Peritoneal Neoplasms - genetics Peritoneal Neoplasms - secondary Peritoneal Neoplasms - surgery Peritoneum Prognosis Stomach Neoplasms - blood Stomach Neoplasms - genetics Stomach Neoplasms - pathology Stomach Neoplasms - surgery Survival analysis Survival Rate THBS1 gene Thrombospondin Thrombospondin 1 - blood Thrombospondin 1 - genetics Tumorigenesis |
| title | Circulating methylated THBS1 DNAs as a novel marker for predicting peritoneal dissemination in gastric cancer |
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