Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications
<p dir="ltr">Triple-negative breast cancer (TNBC) accounts for ~15–20% of breast cancer (BC) and has a higher rate of early relapse and mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) and its signaling pathway have been linked to TNBC. We aimed to inve...
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2019
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| _version_ | 1864513513589833728 |
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| author | Jingxuan Shan (4711089) |
| author2 | Aziz Chouchane (8089028) Younes Mokrab (6367) Mohamad Saad (214545) Salha Boujassoum (8089031) Rosalyn W. Sayaman (8089034) Elad Ziv (1263) Noureddine Bouaouina (61837) Yasmine Remadi (8089037) Sallouha Gabbouj (8089040) Jessica Roelands (7516439) Xiaojing Ma (44943) Davide Bedognetti (2632474) Lotfi Chouchane (61840) |
| author2_role | author author author author author author author author author author author author author |
| author_facet | Jingxuan Shan (4711089) Aziz Chouchane (8089028) Younes Mokrab (6367) Mohamad Saad (214545) Salha Boujassoum (8089031) Rosalyn W. Sayaman (8089034) Elad Ziv (1263) Noureddine Bouaouina (61837) Yasmine Remadi (8089037) Sallouha Gabbouj (8089040) Jessica Roelands (7516439) Xiaojing Ma (44943) Davide Bedognetti (2632474) Lotfi Chouchane (61840) |
| author_role | author |
| dc.creator.none.fl_str_mv | Jingxuan Shan (4711089) Aziz Chouchane (8089028) Younes Mokrab (6367) Mohamad Saad (214545) Salha Boujassoum (8089031) Rosalyn W. Sayaman (8089034) Elad Ziv (1263) Noureddine Bouaouina (61837) Yasmine Remadi (8089037) Sallouha Gabbouj (8089040) Jessica Roelands (7516439) Xiaojing Ma (44943) Davide Bedognetti (2632474) Lotfi Chouchane (61840) |
| dc.date.none.fl_str_mv | 2019-12-06T03:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fonc.2019.01328 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Genetic_Variation_in_CCL5_Signaling_Genes_and_Triple_Negative_Breast_Cancer_Susceptibility_and_Prognosis_Implications/25908370 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Oncology and carcinogenesis CCL5 CCL5 signaling genes triple negative breast cancer prognosis susceptibility |
| dc.title.none.fl_str_mv | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Triple-negative breast cancer (TNBC) accounts for ~15–20% of breast cancer (BC) and has a higher rate of early relapse and mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) and its signaling pathway have been linked to TNBC. We aimed to investigate the susceptibility and prognostic implications of genetic variation in CCL5 signaling genes in TNBC in the present study. We characterized variants in <i>CCL5</i> and that of six other CCL5 signaling genes (<i>CCND1, ZMIZ1, CASP8, NOTCH2, MAP3K21, and HS6ST3</i>) among 1,082 unrelated Tunisian subjects (544 BC patients, including 196 TNBC, and 538 healthy controls), assessed the association of the variants with BC-specific overall survival (OVS) and progression-free survival (PFS), and correlated CCL5 mRNA and serum levels with <i>CCL5</i> genotypes. We found a highly significant association between the <b><i>CCND1</i></b><b> </b><b>rs614367-TT</b> genotype (OR = 5.14; <i>P</i> = 0.004) and TNBC risk, and identified a significant association between the <b>rs614367-T</b> allele and decreased PFS in TNBC. A decreased risk of lymph node metastasis was associated with the <b><i>MAP3K21</i></b><b> </b><b>rs1294255-C</b> allele, particularly in <b>rs1294255-GC</b> (OR = 0.47; <i>P</i> = 0.001). <i>CCL5</i> variants (<b>rs2107538</b> and <b>rs2280789</b>) were linked to CCL5 serum and mRNA levels. In the TCGA TNBC/Basal-like cohort the <b><i>MAP3K21</i></b><b> </b><b>rs1294255-G</b> allele was associated with a decreased OVS. High expression of <i>CCL5</i> in breast tumors was significantly associated with an increased OVS in all BC patients, but particularly in TNBC/Basal-like patients. In conclusion, genetic variation in CCL5 signaling genes may predict not only TNBC risk but also disease aggressiveness.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fonc.2019.01328" target="_blank">https://dx.doi.org/10.3389/fonc.2019.01328</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_d47d62f809dbc8210906b5f0b817b654 |
| identifier_str_mv | 10.3389/fonc.2019.01328 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/25908370 |
| publishDate | 2019 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis ImplicationsJingxuan Shan (4711089)Aziz Chouchane (8089028)Younes Mokrab (6367)Mohamad Saad (214545)Salha Boujassoum (8089031)Rosalyn W. Sayaman (8089034)Elad Ziv (1263)Noureddine Bouaouina (61837)Yasmine Remadi (8089037)Sallouha Gabbouj (8089040)Jessica Roelands (7516439)Xiaojing Ma (44943)Davide Bedognetti (2632474)Lotfi Chouchane (61840)Biomedical and clinical sciencesOncology and carcinogenesisCCL5CCL5 signaling genestriple negative breast cancerprognosissusceptibility<p dir="ltr">Triple-negative breast cancer (TNBC) accounts for ~15–20% of breast cancer (BC) and has a higher rate of early relapse and mortality compared to other subtypes. The Chemokine (C-C motif) ligand 5 (CCL5) and its signaling pathway have been linked to TNBC. We aimed to investigate the susceptibility and prognostic implications of genetic variation in CCL5 signaling genes in TNBC in the present study. We characterized variants in <i>CCL5</i> and that of six other CCL5 signaling genes (<i>CCND1, ZMIZ1, CASP8, NOTCH2, MAP3K21, and HS6ST3</i>) among 1,082 unrelated Tunisian subjects (544 BC patients, including 196 TNBC, and 538 healthy controls), assessed the association of the variants with BC-specific overall survival (OVS) and progression-free survival (PFS), and correlated CCL5 mRNA and serum levels with <i>CCL5</i> genotypes. We found a highly significant association between the <b><i>CCND1</i></b><b> </b><b>rs614367-TT</b> genotype (OR = 5.14; <i>P</i> = 0.004) and TNBC risk, and identified a significant association between the <b>rs614367-T</b> allele and decreased PFS in TNBC. A decreased risk of lymph node metastasis was associated with the <b><i>MAP3K21</i></b><b> </b><b>rs1294255-C</b> allele, particularly in <b>rs1294255-GC</b> (OR = 0.47; <i>P</i> = 0.001). <i>CCL5</i> variants (<b>rs2107538</b> and <b>rs2280789</b>) were linked to CCL5 serum and mRNA levels. In the TCGA TNBC/Basal-like cohort the <b><i>MAP3K21</i></b><b> </b><b>rs1294255-G</b> allele was associated with a decreased OVS. High expression of <i>CCL5</i> in breast tumors was significantly associated with an increased OVS in all BC patients, but particularly in TNBC/Basal-like patients. In conclusion, genetic variation in CCL5 signaling genes may predict not only TNBC risk but also disease aggressiveness.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Oncology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fonc.2019.01328" target="_blank">https://dx.doi.org/10.3389/fonc.2019.01328</a></p>2019-12-06T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fonc.2019.01328https://figshare.com/articles/journal_contribution/Genetic_Variation_in_CCL5_Signaling_Genes_and_Triple_Negative_Breast_Cancer_Susceptibility_and_Prognosis_Implications/25908370CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/259083702019-12-06T03:00:00Z |
| spellingShingle | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications Jingxuan Shan (4711089) Biomedical and clinical sciences Oncology and carcinogenesis CCL5 CCL5 signaling genes triple negative breast cancer prognosis susceptibility |
| status_str | publishedVersion |
| title | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| title_full | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| title_fullStr | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| title_full_unstemmed | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| title_short | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| title_sort | Genetic Variation in CCL5 Signaling Genes and Triple Negative Breast Cancer: Susceptibility and Prognosis Implications |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis CCL5 CCL5 signaling genes triple negative breast cancer prognosis susceptibility |