Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors
: The up-regulation of a telomere maintenance mechanism (TMM) is a common feature of cancer cells and a hallmark of cancer. Routine methods for detecting TMMs in tumor samples are still missing, whereas telomerase targeting treatments are becoming available. In paediatric cancers, alternative length...
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| Veröffentlicht in: | Cancers 2020-04, Vol.12 (4), p.1028 |
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| creator | Idilli, Aurora Irene Pagani, Francesca Kerschbamer, Emanuela Berardinelli, Francesco Bernabé, Manuel Cayuela, María Luisa Piazza, Silvano Poliani, Pietro Luigi Cusanelli, Emilio Mione, Maria Caterina |
| description | : The up-regulation of a telomere maintenance mechanism (TMM) is a common feature of cancer cells and a hallmark of cancer. Routine methods for detecting TMMs in tumor samples are still missing, whereas telomerase targeting treatments are becoming available. In paediatric cancers, alternative lengthening of telomeres (ALT) is found in a subset of sarcomas and malignant brain tumors. ALT is a non-canonical mechanism of telomere maintenance developed by cancer cells with no-functional telomerase.
: To identify drivers and/or markers of ALT, we performed a differential gene expression analysis between two zebrafish models of juvenile brain tumors, that differ only for the telomere maintenance mechanism adopted by tumor cells: one is ALT while the other is telomerase-dependent.
: Comparative analysis of gene expression identified five genes of the pre-replicative complex,
,
and
as upregulated in ALT. We searched for a correlation between telomerase levels and expression of the pre-replicative complex genes in a cohort of paediatric brain cancers and identified a counter-correlation between telomerase expression and the genes of the pre-replicative complex. Moreover, the analysis of ALT markers in a group of 20 patients confirmed the association between ALT and increased RPA and decreased H3K9
localization at telomeres.
: Our study suggests that telomere maintenance mechanisms may act as a driver of telomeric DNA replication and chromatin status in brain cancers and identifies markers of ALT that could be exploited for precise prognostic and therapeutic purposes. |
| doi_str_mv | 10.3390/cancers12041028 |
| format | Article |
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: To identify drivers and/or markers of ALT, we performed a differential gene expression analysis between two zebrafish models of juvenile brain tumors, that differ only for the telomere maintenance mechanism adopted by tumor cells: one is ALT while the other is telomerase-dependent.
: Comparative analysis of gene expression identified five genes of the pre-replicative complex,
,
and
as upregulated in ALT. We searched for a correlation between telomerase levels and expression of the pre-replicative complex genes in a cohort of paediatric brain cancers and identified a counter-correlation between telomerase expression and the genes of the pre-replicative complex. Moreover, the analysis of ALT markers in a group of 20 patients confirmed the association between ALT and increased RPA and decreased H3K9
localization at telomeres.
: Our study suggests that telomere maintenance mechanisms may act as a driver of telomeric DNA replication and chromatin status in brain cancers and identifies markers of ALT that could be exploited for precise prognostic and therapeutic purposes.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers12041028</identifier><identifier>PMID: 32331249</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Brain cancer ; Brain tumors ; Cancer ; Cdc45 protein ; Cell cycle ; Chromatin ; Comparative analysis ; Deoxyribonucleic acid ; DNA ; DNA biosynthesis ; Gene expression ; Localization ; Medical prognosis ; Mutation ; Pediatrics ; Principal components analysis ; Telomerase ; Telomerase reverse transcriptase ; Telomeres ; Therapeutic applications ; Tumor cells ; Tumors</subject><ispartof>Cancers, 2020-04, Vol.12 (4), p.1028</ispartof><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/3.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 by the authors. 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-fd6d72c0491a08650fd4bf2421fe3b22b0403584db1d07aae0a44cd8646715cd3</citedby><cites>FETCH-LOGICAL-c421t-fd6d72c0491a08650fd4bf2421fe3b22b0403584db1d07aae0a44cd8646715cd3</cites><orcidid>0000-0002-1671-5671 ; 0000-0002-3094-4139 ; 0000-0002-2021-9822 ; 0000-0003-4334-0059 ; 0000-0002-5662-8978 ; 0000-0002-7683-8542 ; 0000-0002-2243-629X ; 0000-0002-7156-5434 ; 0000-0002-9040-3705</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/PMC7226177/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226177/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32331249$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Idilli, Aurora Irene</creatorcontrib><creatorcontrib>Pagani, Francesca</creatorcontrib><creatorcontrib>Kerschbamer, Emanuela</creatorcontrib><creatorcontrib>Berardinelli, Francesco</creatorcontrib><creatorcontrib>Bernabé, Manuel</creatorcontrib><creatorcontrib>Cayuela, María Luisa</creatorcontrib><creatorcontrib>Piazza, Silvano</creatorcontrib><creatorcontrib>Poliani, Pietro Luigi</creatorcontrib><creatorcontrib>Cusanelli, Emilio</creatorcontrib><creatorcontrib>Mione, Maria Caterina</creatorcontrib><title>Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors</title><title>Cancers</title><addtitle>Cancers (Basel)</addtitle><description>: The up-regulation of a telomere maintenance mechanism (TMM) is a common feature of cancer cells and a hallmark of cancer. Routine methods for detecting TMMs in tumor samples are still missing, whereas telomerase targeting treatments are becoming available. In paediatric cancers, alternative lengthening of telomeres (ALT) is found in a subset of sarcomas and malignant brain tumors. ALT is a non-canonical mechanism of telomere maintenance developed by cancer cells with no-functional telomerase.
: To identify drivers and/or markers of ALT, we performed a differential gene expression analysis between two zebrafish models of juvenile brain tumors, that differ only for the telomere maintenance mechanism adopted by tumor cells: one is ALT while the other is telomerase-dependent.
: Comparative analysis of gene expression identified five genes of the pre-replicative complex,
,
and
as upregulated in ALT. We searched for a correlation between telomerase levels and expression of the pre-replicative complex genes in a cohort of paediatric brain cancers and identified a counter-correlation between telomerase expression and the genes of the pre-replicative complex. Moreover, the analysis of ALT markers in a group of 20 patients confirmed the association between ALT and increased RPA and decreased H3K9
localization at telomeres.
: Our study suggests that telomere maintenance mechanisms may act as a driver of telomeric DNA replication and chromatin status in brain cancers and identifies markers of ALT that could be exploited for precise prognostic and therapeutic purposes.</description><subject>Brain cancer</subject><subject>Brain tumors</subject><subject>Cancer</subject><subject>Cdc45 protein</subject><subject>Cell cycle</subject><subject>Chromatin</subject><subject>Comparative analysis</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA biosynthesis</subject><subject>Gene expression</subject><subject>Localization</subject><subject>Medical prognosis</subject><subject>Mutation</subject><subject>Pediatrics</subject><subject>Principal components analysis</subject><subject>Telomerase</subject><subject>Telomerase reverse transcriptase</subject><subject>Telomeres</subject><subject>Therapeutic applications</subject><subject>Tumor cells</subject><subject>Tumors</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1r3DAQxUVpaUKac25F0EsvTvS1kn0ppMvmAxYagnMWsjTOKtiSK9kh_e-rsGlIM5cZeL95zPAQOqHklPOGnFkTLKRMGRGUsPoDOmREsUrKRnx8Mx-g45wfSCnOqZLqMzrgrIxMNIeoW-9MuIeMfcDzDvDmaUqQs48Bxx7fJKhuYRq8NbN_BLyO4zTAE76EsF_ZtZvbFpvg8Pm2xTfgvJmTt_hnMkVtlzGm_AV96s2Q4filH6G7i027vqq2vy6v1-fbygpG56p30ilmiWioIbVckd6JrmdF64F3jHVEEL6qheuoI8oYIEYI62oppKIr6_gR-rH3nZZuBGchzMkMekp-NOmPjsbr_5Xgd_o-PmrFmKRKFYPvLwYp_l4gz3r02cIwmABxyZrxRtSqpoIX9Ns79CEuKZT3nqkV4YoRWaizPWVTzDlB_3oMJfo5Qv0uwrLx9e0Pr_y_wPhf_luXsQ</recordid><startdate>20200422</startdate><enddate>20200422</enddate><creator>Idilli, Aurora Irene</creator><creator>Pagani, Francesca</creator><creator>Kerschbamer, Emanuela</creator><creator>Berardinelli, Francesco</creator><creator>Bernabé, Manuel</creator><creator>Cayuela, María Luisa</creator><creator>Piazza, Silvano</creator><creator>Poliani, Pietro Luigi</creator><creator>Cusanelli, Emilio</creator><creator>Mione, Maria Caterina</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1671-5671</orcidid><orcidid>https://orcid.org/0000-0002-3094-4139</orcidid><orcidid>https://orcid.org/0000-0002-2021-9822</orcidid><orcidid>https://orcid.org/0000-0003-4334-0059</orcidid><orcidid>https://orcid.org/0000-0002-5662-8978</orcidid><orcidid>https://orcid.org/0000-0002-7683-8542</orcidid><orcidid>https://orcid.org/0000-0002-2243-629X</orcidid><orcidid>https://orcid.org/0000-0002-7156-5434</orcidid><orcidid>https://orcid.org/0000-0002-9040-3705</orcidid></search><sort><creationdate>20200422</creationdate><title>Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors</title><author>Idilli, Aurora Irene ; Pagani, Francesca ; Kerschbamer, Emanuela ; Berardinelli, Francesco ; Bernabé, Manuel ; Cayuela, María Luisa ; Piazza, Silvano ; Poliani, Pietro Luigi ; Cusanelli, Emilio ; Mione, Maria Caterina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-fd6d72c0491a08650fd4bf2421fe3b22b0403584db1d07aae0a44cd8646715cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Brain cancer</topic><topic>Brain tumors</topic><topic>Cancer</topic><topic>Cdc45 protein</topic><topic>Cell cycle</topic><topic>Chromatin</topic><topic>Comparative analysis</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA biosynthesis</topic><topic>Gene expression</topic><topic>Localization</topic><topic>Medical prognosis</topic><topic>Mutation</topic><topic>Pediatrics</topic><topic>Principal components analysis</topic><topic>Telomerase</topic><topic>Telomerase reverse transcriptase</topic><topic>Telomeres</topic><topic>Therapeutic applications</topic><topic>Tumor cells</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Idilli, Aurora Irene</creatorcontrib><creatorcontrib>Pagani, Francesca</creatorcontrib><creatorcontrib>Kerschbamer, Emanuela</creatorcontrib><creatorcontrib>Berardinelli, Francesco</creatorcontrib><creatorcontrib>Bernabé, Manuel</creatorcontrib><creatorcontrib>Cayuela, María Luisa</creatorcontrib><creatorcontrib>Piazza, Silvano</creatorcontrib><creatorcontrib>Poliani, Pietro Luigi</creatorcontrib><creatorcontrib>Cusanelli, Emilio</creatorcontrib><creatorcontrib>Mione, Maria Caterina</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</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>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancers</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Idilli, Aurora Irene</au><au>Pagani, Francesca</au><au>Kerschbamer, Emanuela</au><au>Berardinelli, Francesco</au><au>Bernabé, Manuel</au><au>Cayuela, María Luisa</au><au>Piazza, Silvano</au><au>Poliani, Pietro Luigi</au><au>Cusanelli, Emilio</au><au>Mione, Maria Caterina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors</atitle><jtitle>Cancers</jtitle><addtitle>Cancers (Basel)</addtitle><date>2020-04-22</date><risdate>2020</risdate><volume>12</volume><issue>4</issue><spage>1028</spage><pages>1028-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>: The up-regulation of a telomere maintenance mechanism (TMM) is a common feature of cancer cells and a hallmark of cancer. Routine methods for detecting TMMs in tumor samples are still missing, whereas telomerase targeting treatments are becoming available. In paediatric cancers, alternative lengthening of telomeres (ALT) is found in a subset of sarcomas and malignant brain tumors. ALT is a non-canonical mechanism of telomere maintenance developed by cancer cells with no-functional telomerase.
: To identify drivers and/or markers of ALT, we performed a differential gene expression analysis between two zebrafish models of juvenile brain tumors, that differ only for the telomere maintenance mechanism adopted by tumor cells: one is ALT while the other is telomerase-dependent.
: Comparative analysis of gene expression identified five genes of the pre-replicative complex,
,
and
as upregulated in ALT. We searched for a correlation between telomerase levels and expression of the pre-replicative complex genes in a cohort of paediatric brain cancers and identified a counter-correlation between telomerase expression and the genes of the pre-replicative complex. Moreover, the analysis of ALT markers in a group of 20 patients confirmed the association between ALT and increased RPA and decreased H3K9
localization at telomeres.
: Our study suggests that telomere maintenance mechanisms may act as a driver of telomeric DNA replication and chromatin status in brain cancers and identifies markers of ALT that could be exploited for precise prognostic and therapeutic purposes.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>32331249</pmid><doi>10.3390/cancers12041028</doi><orcidid>https://orcid.org/0000-0002-1671-5671</orcidid><orcidid>https://orcid.org/0000-0002-3094-4139</orcidid><orcidid>https://orcid.org/0000-0002-2021-9822</orcidid><orcidid>https://orcid.org/0000-0003-4334-0059</orcidid><orcidid>https://orcid.org/0000-0002-5662-8978</orcidid><orcidid>https://orcid.org/0000-0002-7683-8542</orcidid><orcidid>https://orcid.org/0000-0002-2243-629X</orcidid><orcidid>https://orcid.org/0000-0002-7156-5434</orcidid><orcidid>https://orcid.org/0000-0002-9040-3705</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MDPI - Multidisciplinary Digital Publishing Institute; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access |
| subjects | Brain cancer Brain tumors Cancer Cdc45 protein Cell cycle Chromatin Comparative analysis Deoxyribonucleic acid DNA DNA biosynthesis Gene expression Localization Medical prognosis Mutation Pediatrics Principal components analysis Telomerase Telomerase reverse transcriptase Telomeres Therapeutic applications Tumor cells Tumors |
| title | Changes in the Expression of Pre-Replicative Complex Genes in hTERT and ALT Pediatric Brain Tumors |
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