Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes
Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/6/651 |
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| author | Concetta Saponaro Annarita Fanizzi Margherita Sonnessa Paolo Mondelli Daniele Vergara Donato Loisi Raffaella Massafra Agnese Latorre Francesco A. Zito Laura Schirosi |
| author_facet | Concetta Saponaro Annarita Fanizzi Margherita Sonnessa Paolo Mondelli Daniele Vergara Donato Loisi Raffaella Massafra Agnese Latorre Francesco A. Zito Laura Schirosi |
| author_sort | Concetta Saponaro |
| collection | DOAJ |
| description | Inflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and <i>MYC</i> ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (<i>p</i> < 0.0001). NLRP3, PYCARD and CyclinD1’s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (<i>p</i> < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (<i>p</i> = 0.017 and <i>p</i> = 0.0015, respectively). The association NLRP3+/<i>CCND1+</i> or PYCARD+/<i>CCND1+</i> was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/<i>CCND1−</i> or PYCARD+/<i>CCND1−</i> patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of <i>CCND1</i> results in Luminal subtype BC’ss poor prognosis. |
| first_indexed | 2024-03-09T22:47:11Z |
| format | Article |
| id | doaj.art-30f836eaad17433698bbc277a5b2fc64 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T22:47:11Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-30f836eaad17433698bbc277a5b2fc642023-11-23T18:26:20ZengMDPI AGPharmaceuticals1424-82472022-05-0115665110.3390/ph15060651Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer SubtypesConcetta Saponaro0Annarita Fanizzi1Margherita Sonnessa2Paolo Mondelli3Daniele Vergara4Donato Loisi5Raffaella Massafra6Agnese Latorre7Francesco A. Zito8Laura Schirosi9Pathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyDepartment of Health Physics, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyPathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyPathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyDepartment of Biological and Environmental Sciences and Technologies (DiSTeBA), University of Salento, 73100 Lecce, ItalyPathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyDepartment of Health Physics, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyMedical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyPathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyPathology Department, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, ItalyInflammasomes are protein complexes involved in the regulation of different biological conditions. Over the past few years, the role of NLRP3 in different tumor types has gained interest. In breast cancer (BC), NLRP3 has been associated with multiple processes including epithelia mesenchymal transition, invasion and metastization. Little is known about molecular modifications of NLRP3 up-regulation. In this study, in a cohort of BCs, the expression levels of NLRP3 and PYCARD were analyzed in combination with CyclinD1 and <i>MYC</i> ones and their gene alterations. We described a correlation between the NLRP3/PYCARD axis and CyclinD1 (<i>p</i> < 0.0001). NLRP3, PYCARD and CyclinD1’s positive expression was observed in estrogen receptor (ER) and progesterone receptor (PgR) positive cases (<i>p</i> < 0.0001). Furthermore, a reduction of NLRP3 and PYCARD expression has been observed in triple negative breast cancers (TNBCs) with respect to the Luminal phenotypes (<i>p</i> = 0.017 and <i>p</i> = 0.0015, respectively). The association NLRP3+/<i>CCND1+</i> or PYCARD+/<i>CCND1+</i> was related to more aggressive clinicopathological characteristics and a worse clinical outcome, both for progression free survival (PFS) and overall survival (OS) with respect to NLRP3+/<i>CCND1−</i> or PYCARD+/<i>CCND1−</i> patients, both in the whole cohort and also in the subset of Luminal tumors. In conclusion, our study shows that the NLRP3 inflammasome complex is down-regulated in TNBC compared to the Luminal subgroup. Moreover, the expression levels of NLRP3 and PYCARD together with the alterations of <i>CCND1</i> results in Luminal subtype BC’ss poor prognosis.https://www.mdpi.com/1424-8247/15/6/651inflammasome NLRP3PYCARDCyclinD1MYC<i>CCND1</i><i>MYC</i> |
| spellingShingle | Concetta Saponaro Annarita Fanizzi Margherita Sonnessa Paolo Mondelli Daniele Vergara Donato Loisi Raffaella Massafra Agnese Latorre Francesco A. Zito Laura Schirosi Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes Pharmaceuticals inflammasome NLRP3 PYCARD CyclinD1 MYC <i>CCND1</i> <i>MYC</i> |
| title | Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes |
| title_full | Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes |
| title_fullStr | Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes |
| title_full_unstemmed | Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes |
| title_short | Downstream Signaling of Inflammasome Pathway Affects Patients’ Outcome in the Context of Distinct Molecular Breast Cancer Subtypes |
| title_sort | downstream signaling of inflammasome pathway affects patients outcome in the context of distinct molecular breast cancer subtypes |
| topic | inflammasome NLRP3 PYCARD CyclinD1 MYC <i>CCND1</i> <i>MYC</i> |
| url | https://www.mdpi.com/1424-8247/15/6/651 |
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