Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis
Background This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC). Methods and Results The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients....
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| Veröffentlicht in: | Molecular biology reports 2022-12, Vol.49 (12), p.11243-11253 |
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| creator | Ak Aksoy, Secil Tunca, Berrin Erçelik, Melis Tezcan, Gulcin Ozturk, Ersin Cecener, Gulsah Ugras, Nesrin Yilmazlar, Tuncay Yerci, Omer |
| description | Background
This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC).
Methods and Results
The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages.
Results
High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells.
Conclusion
MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance. |
| doi_str_mv | 10.1007/s11033-022-07680-y |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2742894377</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2849888548</sourcerecordid><originalsourceid>FETCH-LOGICAL-c315t-555958ceb4947afb4dab6d533f01b6d2492f647a783fade6298f1607963cd2bb3</originalsourceid><addsrcrecordid>eNp9kU1LxDAQhoMouK7-AU8BL16i-WzS47KsH7DiZT2HNE23WbrtmrRo8c8brSB48DTDzPO-zPACcEnwDcFY3kZCMGMIU4qwzBRG4xGYESEZ4rlUx2CGGSaIK0FOwVmMO4wxJ1LMwMfKhGZEsTdbB23XdC20prUuwDff17D22xo-LdaLDYHu_RBcjD4hPkITY2e96V05kX3toEB3zdCFbgjG-gYm2ifj5AZNW8Jq6Ifg4N71Jk3T6hycVKaJ7uKnzsHL3WqzfEDr5_vH5WKNLCOiR0KIXCjrCp5zaaqCl6bISsFYhUlqKM9plaWNVKwypctoriqSYZlnzJa0KNgcXE--h9C9Di72eu-jdU1jWtcNUVPFc6WU4CqhV3_QXfqmTddpKjlVOWdSJopOlA1djMFV-hD83oRRE6y_8tBTHjrlob_z0GMSsUkUE9xuXfi1_kf1CX-Hj0A</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2742894377</pqid></control><display><type>article</type><title>Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis</title><source>SpringerLink Journals</source><creator>Ak Aksoy, Secil ; Tunca, Berrin ; Erçelik, Melis ; Tezcan, Gulcin ; Ozturk, Ersin ; Cecener, Gulsah ; Ugras, Nesrin ; Yilmazlar, Tuncay ; Yerci, Omer</creator><creatorcontrib>Ak Aksoy, Secil ; Tunca, Berrin ; Erçelik, Melis ; Tezcan, Gulcin ; Ozturk, Ersin ; Cecener, Gulsah ; Ugras, Nesrin ; Yilmazlar, Tuncay ; Yerci, Omer</creatorcontrib><description>Background
This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC).
Methods and Results
The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages.
Results
High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells.
Conclusion
MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.</description><identifier>ISSN: 0301-4851</identifier><identifier>EISSN: 1573-4978</identifier><identifier>DOI: 10.1007/s11033-022-07680-y</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>5-Fluorouracil ; Animal Anatomy ; Animal Biochemistry ; Annexin V ; biomarkers ; Biomedical and Life Sciences ; colon ; Colon cancer ; Colonies ; Colorectal cancer ; colorectal neoplasms ; fluorouracil ; Histology ; Invasiveness ; Life Sciences ; Metastases ; Metastasis ; Morphology ; mRNA ; Non-coding RNA ; Original Article ; Patients ; Regulatory non-coding RNAs in health and disease ; relapse ; therapeutics ; Tumors ; Wound healing</subject><ispartof>Molecular biology reports, 2022-12, Vol.49 (12), p.11243-11253</ispartof><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2022</rights><rights>The Author(s), under exclusive licence to Springer Nature B.V. 2022.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c315t-555958ceb4947afb4dab6d533f01b6d2492f647a783fade6298f1607963cd2bb3</citedby><cites>FETCH-LOGICAL-c315t-555958ceb4947afb4dab6d533f01b6d2492f647a783fade6298f1607963cd2bb3</cites><orcidid>0000-0002-1619-6680</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s11033-022-07680-y$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s11033-022-07680-y$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids></links><search><creatorcontrib>Ak Aksoy, Secil</creatorcontrib><creatorcontrib>Tunca, Berrin</creatorcontrib><creatorcontrib>Erçelik, Melis</creatorcontrib><creatorcontrib>Tezcan, Gulcin</creatorcontrib><creatorcontrib>Ozturk, Ersin</creatorcontrib><creatorcontrib>Cecener, Gulsah</creatorcontrib><creatorcontrib>Ugras, Nesrin</creatorcontrib><creatorcontrib>Yilmazlar, Tuncay</creatorcontrib><creatorcontrib>Yerci, Omer</creatorcontrib><title>Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis</title><title>Molecular biology reports</title><addtitle>Mol Biol Rep</addtitle><description>Background
This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC).
Methods and Results
The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages.
Results
High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells.
Conclusion
MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.</description><subject>5-Fluorouracil</subject><subject>Animal Anatomy</subject><subject>Animal Biochemistry</subject><subject>Annexin V</subject><subject>biomarkers</subject><subject>Biomedical and Life Sciences</subject><subject>colon</subject><subject>Colon cancer</subject><subject>Colonies</subject><subject>Colorectal cancer</subject><subject>colorectal neoplasms</subject><subject>fluorouracil</subject><subject>Histology</subject><subject>Invasiveness</subject><subject>Life Sciences</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Morphology</subject><subject>mRNA</subject><subject>Non-coding RNA</subject><subject>Original Article</subject><subject>Patients</subject><subject>Regulatory non-coding RNAs in health and disease</subject><subject>relapse</subject><subject>therapeutics</subject><subject>Tumors</subject><subject>Wound healing</subject><issn>0301-4851</issn><issn>1573-4978</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kU1LxDAQhoMouK7-AU8BL16i-WzS47KsH7DiZT2HNE23WbrtmrRo8c8brSB48DTDzPO-zPACcEnwDcFY3kZCMGMIU4qwzBRG4xGYESEZ4rlUx2CGGSaIK0FOwVmMO4wxJ1LMwMfKhGZEsTdbB23XdC20prUuwDff17D22xo-LdaLDYHu_RBcjD4hPkITY2e96V05kX3toEB3zdCFbgjG-gYm2ifj5AZNW8Jq6Ifg4N71Jk3T6hycVKaJ7uKnzsHL3WqzfEDr5_vH5WKNLCOiR0KIXCjrCp5zaaqCl6bISsFYhUlqKM9plaWNVKwypctoriqSYZlnzJa0KNgcXE--h9C9Di72eu-jdU1jWtcNUVPFc6WU4CqhV3_QXfqmTddpKjlVOWdSJopOlA1djMFV-hD83oRRE6y_8tBTHjrlob_z0GMSsUkUE9xuXfi1_kf1CX-Hj0A</recordid><startdate>20221201</startdate><enddate>20221201</enddate><creator>Ak Aksoy, Secil</creator><creator>Tunca, Berrin</creator><creator>Erçelik, Melis</creator><creator>Tezcan, Gulcin</creator><creator>Ozturk, Ersin</creator><creator>Cecener, Gulsah</creator><creator>Ugras, Nesrin</creator><creator>Yilmazlar, Tuncay</creator><creator>Yerci, Omer</creator><general>Springer Netherlands</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</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>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>RC3</scope><scope>7S9</scope><scope>L.6</scope><orcidid>https://orcid.org/0000-0002-1619-6680</orcidid></search><sort><creationdate>20221201</creationdate><title>Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis</title><author>Ak Aksoy, Secil ; Tunca, Berrin ; Erçelik, Melis ; Tezcan, Gulcin ; Ozturk, Ersin ; Cecener, Gulsah ; Ugras, Nesrin ; Yilmazlar, Tuncay ; Yerci, Omer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c315t-555958ceb4947afb4dab6d533f01b6d2492f647a783fade6298f1607963cd2bb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>5-Fluorouracil</topic><topic>Animal Anatomy</topic><topic>Animal Biochemistry</topic><topic>Annexin V</topic><topic>biomarkers</topic><topic>Biomedical and Life Sciences</topic><topic>colon</topic><topic>Colon cancer</topic><topic>Colonies</topic><topic>Colorectal cancer</topic><topic>colorectal neoplasms</topic><topic>fluorouracil</topic><topic>Histology</topic><topic>Invasiveness</topic><topic>Life Sciences</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Morphology</topic><topic>mRNA</topic><topic>Non-coding RNA</topic><topic>Original Article</topic><topic>Patients</topic><topic>Regulatory non-coding RNAs in health and disease</topic><topic>relapse</topic><topic>therapeutics</topic><topic>Tumors</topic><topic>Wound healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ak Aksoy, Secil</creatorcontrib><creatorcontrib>Tunca, Berrin</creatorcontrib><creatorcontrib>Erçelik, Melis</creatorcontrib><creatorcontrib>Tezcan, Gulcin</creatorcontrib><creatorcontrib>Ozturk, Ersin</creatorcontrib><creatorcontrib>Cecener, Gulsah</creatorcontrib><creatorcontrib>Ugras, Nesrin</creatorcontrib><creatorcontrib>Yilmazlar, Tuncay</creatorcontrib><creatorcontrib>Yerci, Omer</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research 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>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Molecular biology reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ak Aksoy, Secil</au><au>Tunca, Berrin</au><au>Erçelik, Melis</au><au>Tezcan, Gulcin</au><au>Ozturk, Ersin</au><au>Cecener, Gulsah</au><au>Ugras, Nesrin</au><au>Yilmazlar, Tuncay</au><au>Yerci, Omer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis</atitle><jtitle>Molecular biology reports</jtitle><stitle>Mol Biol Rep</stitle><date>2022-12-01</date><risdate>2022</risdate><volume>49</volume><issue>12</issue><spage>11243</spage><epage>11253</epage><pages>11243-11253</pages><issn>0301-4851</issn><eissn>1573-4978</eissn><abstract>Background
This study aimed to investigate the role of long noncoding RNA (LncRNA) expression profiles to predict relapse and 5-FU response in patients with stage I/II colon cancer (CC).
Methods and Results
The expression level of 15 LncRNA was analyzed in stage I/II colon tumors of 126 CC patients. To confirm the findings in-vitro, 5FU-resistant HT29 cells were generated by subjecting HT-29 cells to the increasing concentrations of 5FU for 6 months. The 5FU resistance was observed in WST-1 and Annexin V analyses. The colony formation and wound healing assays were assessed to determine the metastatic properties of the cells. Expression levels of LncRNAs and mRNA of EMT-related genes were determined by RT-PCR. The role of LncRNA on metastasis and 5FU sensitivity were confirmed in pcDNA3.0-PTENP1 and si-MALAT1 expressed 5FU-resistant HT29 cell lineages.
Results
High MALAT1 (p = 0.0002) and low PTENP1 (p = 0.0044) expressions were significantly associated with 5-FU resistance and tumor relapse in stage I/II CC. The invasiveness and colony-forming characteristics of 5-FU-resistant cell lineages were higher as compared to the parent HT-29. Moreover, the expression of MALAT1 (p = 0.0009) was increased while the expression of PTENP1 (p = 0.0158) decreased in 5FU-resistant-HT-29 cells. Si-MALAT1 treatment increased cell sensitivity to 5FU, whereas it decreased invasive behaviors of 5 FU-resistant-HT-29 cells.
Conclusion
MALAT1 may be a biomarker in predicting recurrence in early-stage CC. Our findings suggest that a cell-based therapy to target MALAT1 could be established for these patients to prevent metastasis and 5-FU resistance.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><doi>10.1007/s11033-022-07680-y</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-1619-6680</orcidid></addata></record> |
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| subjects | 5-Fluorouracil Animal Anatomy Animal Biochemistry Annexin V biomarkers Biomedical and Life Sciences colon Colon cancer Colonies Colorectal cancer colorectal neoplasms fluorouracil Histology Invasiveness Life Sciences Metastases Metastasis Morphology mRNA Non-coding RNA Original Article Patients Regulatory non-coding RNAs in health and disease relapse therapeutics Tumors Wound healing |
| title | Early-stage colon cancer with high MALAT1 expression is associated with the 5-Fluorouracil resistance and future metastasis |
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