Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer
Background Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients,...
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| Veröffentlicht in: | Journal of gastrointestinal cancer 2024-09, Vol.55 (3), p.1190-1198 |
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| creator | Ponomaryova, Anastasia A. Rykova, Elena Yu Solovyova, Anastasia I. Tarasova, Anna S. Kostromitsky, Dmitry N. Dobrodeev, Alexey Yu Afanasiev, Sergey A. Cherdyntseva, Nadezhda V. |
| description | Background
Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers.
Purpose
Evaluation of the changes in the methylation level of LINE-1 elements and
SEPTIN9
and
IKZF1
genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up.
Methods
Blood samples were obtained from RC patients (
n
= 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10–15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1,
SEPTIN9
, and
IKZF1
in the csb-cfDNA was evaluated by quantitative methyl-specific PCR.
Results
The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The
SEPTIN9
gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The
IKZF1
gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (
n
= 5) showed an increase in methylation level for the
SEPTIN9
and
IKZF1
genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10–15 days after surgery. There were no changes in the circulating
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (
n
= 20) without relapses.
Conclusion
The results indicate that
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients. |
| doi_str_mv | 10.1007/s12029-024-01066-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3064141914</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3064141914</sourcerecordid><originalsourceid>FETCH-LOGICAL-c298t-d34ecc756a603c921f6ded41dff854c7d95db1f3d0ab7ace1b18d1fe1008c95a3</originalsourceid><addsrcrecordid>eNp9kMtOwzAQRS0EoqXwAyyQl2wCnjycZFmFp9QKCZW15dqTNiVxgp0s8veYFrpkNSPNuVeaQ8g1sDtgLL13ELIwD1gYBwwY58F4QqaQxxBwHvHT4x5mE3Lh3I4xHicA52QSZVmYJxmbEvUwGtlUihZbaTboaGVoUVk11LKvzIYusd-OfkdNl9J-ot0T7-i61jikfUvnpq_6oWktXW3Rym6kbekB1cuaFtIotJfkrJS1w6vfOSMfT4-r4iVYvD2_FvNFoMI86wMdxahUmnDJWaTyEEquUcegyzJLYpXqPNFrKCPN5DqVCmENmYYSvYtM5YmMZuT20NvZ9mtA14umcgrrWhpsByci_z_EkEPs0fCAKts6Z7EUna0aaUcBTPzIFQe5wssVe7li9KGb3_5h3aA-Rv5seiA6AM6fvE0rdu1gjf_5v9pvXg6G6g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3064141914</pqid></control><display><type>article</type><title>Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer</title><source>SpringerLink Journals</source><creator>Ponomaryova, Anastasia A. ; Rykova, Elena Yu ; Solovyova, Anastasia I. ; Tarasova, Anna S. ; Kostromitsky, Dmitry N. ; Dobrodeev, Alexey Yu ; Afanasiev, Sergey A. ; Cherdyntseva, Nadezhda V.</creator><creatorcontrib>Ponomaryova, Anastasia A. ; Rykova, Elena Yu ; Solovyova, Anastasia I. ; Tarasova, Anna S. ; Kostromitsky, Dmitry N. ; Dobrodeev, Alexey Yu ; Afanasiev, Sergey A. ; Cherdyntseva, Nadezhda V.</creatorcontrib><description>Background
Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers.
Purpose
Evaluation of the changes in the methylation level of LINE-1 elements and
SEPTIN9
and
IKZF1
genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up.
Methods
Blood samples were obtained from RC patients (
n
= 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10–15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1,
SEPTIN9
, and
IKZF1
in the csb-cfDNA was evaluated by quantitative methyl-specific PCR.
Results
The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The
SEPTIN9
gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The
IKZF1
gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (
n
= 5) showed an increase in methylation level for the
SEPTIN9
and
IKZF1
genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10–15 days after surgery. There were no changes in the circulating
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (
n
= 20) without relapses.
Conclusion
The results indicate that
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients.</description><identifier>ISSN: 1941-6628</identifier><identifier>ISSN: 1941-6636</identifier><identifier>EISSN: 1941-6636</identifier><identifier>DOI: 10.1007/s12029-024-01066-y</identifier><identifier>PMID: 38829580</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Cancer Research ; Gastroenterology ; Internal Medicine ; Medicine ; Medicine & Public Health ; Oncology ; Radiotherapy</subject><ispartof>Journal of gastrointestinal cancer, 2024-09, Vol.55 (3), p.1190-1198</ispartof><rights>The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c298t-d34ecc756a603c921f6ded41dff854c7d95db1f3d0ab7ace1b18d1fe1008c95a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12029-024-01066-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12029-024-01066-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38829580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ponomaryova, Anastasia A.</creatorcontrib><creatorcontrib>Rykova, Elena Yu</creatorcontrib><creatorcontrib>Solovyova, Anastasia I.</creatorcontrib><creatorcontrib>Tarasova, Anna S.</creatorcontrib><creatorcontrib>Kostromitsky, Dmitry N.</creatorcontrib><creatorcontrib>Dobrodeev, Alexey Yu</creatorcontrib><creatorcontrib>Afanasiev, Sergey A.</creatorcontrib><creatorcontrib>Cherdyntseva, Nadezhda V.</creatorcontrib><title>Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer</title><title>Journal of gastrointestinal cancer</title><addtitle>J Gastrointest Canc</addtitle><addtitle>J Gastrointest Cancer</addtitle><description>Background
Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers.
Purpose
Evaluation of the changes in the methylation level of LINE-1 elements and
SEPTIN9
and
IKZF1
genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up.
Methods
Blood samples were obtained from RC patients (
n
= 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10–15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1,
SEPTIN9
, and
IKZF1
in the csb-cfDNA was evaluated by quantitative methyl-specific PCR.
Results
The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The
SEPTIN9
gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The
IKZF1
gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (
n
= 5) showed an increase in methylation level for the
SEPTIN9
and
IKZF1
genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10–15 days after surgery. There were no changes in the circulating
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (
n
= 20) without relapses.
Conclusion
The results indicate that
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients.</description><subject>Cancer Research</subject><subject>Gastroenterology</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Radiotherapy</subject><issn>1941-6628</issn><issn>1941-6636</issn><issn>1941-6636</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kMtOwzAQRS0EoqXwAyyQl2wCnjycZFmFp9QKCZW15dqTNiVxgp0s8veYFrpkNSPNuVeaQ8g1sDtgLL13ELIwD1gYBwwY58F4QqaQxxBwHvHT4x5mE3Lh3I4xHicA52QSZVmYJxmbEvUwGtlUihZbaTboaGVoUVk11LKvzIYusd-OfkdNl9J-ot0T7-i61jikfUvnpq_6oWktXW3Rym6kbekB1cuaFtIotJfkrJS1w6vfOSMfT4-r4iVYvD2_FvNFoMI86wMdxahUmnDJWaTyEEquUcegyzJLYpXqPNFrKCPN5DqVCmENmYYSvYtM5YmMZuT20NvZ9mtA14umcgrrWhpsByci_z_EkEPs0fCAKts6Z7EUna0aaUcBTPzIFQe5wssVe7li9KGb3_5h3aA-Rv5seiA6AM6fvE0rdu1gjf_5v9pvXg6G6g</recordid><startdate>20240901</startdate><enddate>20240901</enddate><creator>Ponomaryova, Anastasia A.</creator><creator>Rykova, Elena Yu</creator><creator>Solovyova, Anastasia I.</creator><creator>Tarasova, Anna S.</creator><creator>Kostromitsky, Dmitry N.</creator><creator>Dobrodeev, Alexey Yu</creator><creator>Afanasiev, Sergey A.</creator><creator>Cherdyntseva, Nadezhda V.</creator><general>Springer US</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240901</creationdate><title>Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer</title><author>Ponomaryova, Anastasia A. ; Rykova, Elena Yu ; Solovyova, Anastasia I. ; Tarasova, Anna S. ; Kostromitsky, Dmitry N. ; Dobrodeev, Alexey Yu ; Afanasiev, Sergey A. ; Cherdyntseva, Nadezhda V.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c298t-d34ecc756a603c921f6ded41dff854c7d95db1f3d0ab7ace1b18d1fe1008c95a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cancer Research</topic><topic>Gastroenterology</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Radiotherapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ponomaryova, Anastasia A.</creatorcontrib><creatorcontrib>Rykova, Elena Yu</creatorcontrib><creatorcontrib>Solovyova, Anastasia I.</creatorcontrib><creatorcontrib>Tarasova, Anna S.</creatorcontrib><creatorcontrib>Kostromitsky, Dmitry N.</creatorcontrib><creatorcontrib>Dobrodeev, Alexey Yu</creatorcontrib><creatorcontrib>Afanasiev, Sergey A.</creatorcontrib><creatorcontrib>Cherdyntseva, Nadezhda V.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of gastrointestinal cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ponomaryova, Anastasia A.</au><au>Rykova, Elena Yu</au><au>Solovyova, Anastasia I.</au><au>Tarasova, Anna S.</au><au>Kostromitsky, Dmitry N.</au><au>Dobrodeev, Alexey Yu</au><au>Afanasiev, Sergey A.</au><au>Cherdyntseva, Nadezhda V.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer</atitle><jtitle>Journal of gastrointestinal cancer</jtitle><stitle>J Gastrointest Canc</stitle><addtitle>J Gastrointest Cancer</addtitle><date>2024-09-01</date><risdate>2024</risdate><volume>55</volume><issue>3</issue><spage>1190</spage><epage>1198</epage><pages>1190-1198</pages><issn>1941-6628</issn><issn>1941-6636</issn><eissn>1941-6636</eissn><abstract>Background
Rectal cancer (RC) occupies a leading position in the structure of oncological morbidity and mortality. Aberrant methylation of tumor-suppressor genes and hypomethylation of retrotransposons were shown to be detectable in cell-free DNA, circulating in the blood (cfDNA) of cancer patients, indicating the possibility to use them as diagnostic and prognosis markers.
Purpose
Evaluation of the changes in the methylation level of LINE-1 elements and
SEPTIN9
and
IKZF1
genes in the cell-surface-bound cfDNA (csb-cfDNA) from the blood of RC patients after antitumor therapy at a long-term follow-up.
Methods
Blood samples were obtained from RC patients (
n
= 25) before treatment, after preoperative chemotherapy (3 courses according to the XELOX scheme), 10–15 days after surgery, and every 3 months during 12 months of dynamic observation. The methylation level of LINE-1,
SEPTIN9
, and
IKZF1
in the csb-cfDNA was evaluated by quantitative methyl-specific PCR.
Results
The LINE-1 methylation level in the csb-cfDNA increased 1.6 times in RC patients after chemotherapy and 3 times after tumor resection versus methylation level before therapy. The
SEPTIN9
gene methylation level in the csb-cfDNA decreased by 1.7 times in RC patients after chemotherapy and by 2.3 times after tumor resection compared with the values before the treatment. The
IKZF1
gene methylation level decreased by 2 times in RC patients after combined therapy. Notably, all patients with relapses (
n
= 5) showed an increase in methylation level for the
SEPTIN9
and
IKZF1
genes and a decrease of methylation level for the LINE-1 elements by 2 times or more in comparison with the level 10–15 days after surgery. There were no changes in the circulating
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels during the 12-month follow-up period after the combined therapy of RC patients (
n
= 20) without relapses.
Conclusion
The results indicate that
SEPTIN9
,
IKZF1
, and LINE-1 methylation levels in the csb-cfDNA are potential markers of the effectiveness of antitumor therapy and early detection of relapse in RC patients.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>38829580</pmid><doi>10.1007/s12029-024-01066-y</doi><tpages>9</tpages></addata></record> |
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| subjects | Cancer Research Gastroenterology Internal Medicine Medicine Medicine & Public Health Oncology Radiotherapy |
| title | Dynamic Changes in Circulating Methylated Markers in Response to Antitumor Therapy of Rectal Cancer |
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