Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions
<h3 dir="ltr">Background</h3><p dir="ltr">Malignant peritoneal mesothelioma (MPeM) is an aggressive cancer affecting the abdominal peritoneal lining and intra-abdominal organs, with a median survival of ~2.5 years.</p><h3 dir="ltr">Methods&...
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| مؤلفون آخرون: | |
| منشور في: |
2024
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| _version_ | 1864513522512166912 |
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| author | Kalyani B. Karunakaran (12478431) |
| author2 | Madhavi K. Ganapathiraju (12478434) |
| author2_role | author |
| author_facet | Kalyani B. Karunakaran (12478431) Madhavi K. Ganapathiraju (12478434) |
| author_role | author |
| dc.creator.none.fl_str_mv | Kalyani B. Karunakaran (12478431) Madhavi K. Ganapathiraju (12478434) |
| dc.date.none.fl_str_mv | 2024-05-24T15:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1038/s44276-024-00062-w |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Malignant_peritoneal_mesothelioma_interactome_with_417_novel_protein_protein_interactions/31444096 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Genetics Biomedical and clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Gene expression Transcriptomic Molecular pathways Drug repurposing cancer biology |
| dc.title.none.fl_str_mv | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <h3 dir="ltr">Background</h3><p dir="ltr">Malignant peritoneal mesothelioma (MPeM) is an aggressive cancer affecting the abdominal peritoneal lining and intra-abdominal organs, with a median survival of ~2.5 years.</p><h3 dir="ltr">Methods</h3><p dir="ltr">We constructed the protein interactome of 59 MPeM-associated genes with previously known protein-protein interactions (PPIs) as well as novel PPIs predicted using our previously developed HiPPIP computational model and analysed it for transcriptomic and functional associations and for repurposable drugs.</p><h3 dir="ltr">Results</h3><p dir="ltr">The MPeM interactome had over 400 computationally predicted PPIs and 4700 known PPIs. Transcriptomic evidence validated 75.6% of the genes in the interactome and 65% of the novel interactors. Some genes had tissue-specific expression in extramedullary hematopoietic sites and the expression of some genes could be correlated with unfavourable prognoses in various cancers. 39 out of 152 drugs that target the proteins in the interactome were identified as potentially repurposable for MPeM, with 29 having evidence from prior clinical trials, animal models or cell lines for effectiveness against peritoneal and pleural mesothelioma and primary peritoneal cancer. Functional modules related to chromosomal segregation, transcriptional dysregulation, IL-6 production and hematopoiesis were identified from the interactome. The MPeM interactome overlapped significantly with the malignant pleural mesothelioma interactome, revealing shared molecular pathways.</p><h3 dir="ltr">Conclusions</h3><p dir="ltr">Our findings demonstrate the utility of the interactome in uncovering biological associations and in generating clinically translatable results.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: BJC Reports<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/10.1038/s44276-024-00062-w" target="_blank">https://dx.doi.org/10.1038/s44276-024-00062-w</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_5536088e0deac2a4db41fb7cf8a355c0 |
| identifier_str_mv | 10.1038/s44276-024-00062-w |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/31444096 |
| publishDate | 2024 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactionsKalyani B. Karunakaran (12478431)Madhavi K. Ganapathiraju (12478434)Biological sciencesGeneticsBiomedical and clinical sciencesOncology and carcinogenesisPharmacology and pharmaceutical sciencesGene expressionTranscriptomicMolecular pathwaysDrug repurposingcancer biology<h3 dir="ltr">Background</h3><p dir="ltr">Malignant peritoneal mesothelioma (MPeM) is an aggressive cancer affecting the abdominal peritoneal lining and intra-abdominal organs, with a median survival of ~2.5 years.</p><h3 dir="ltr">Methods</h3><p dir="ltr">We constructed the protein interactome of 59 MPeM-associated genes with previously known protein-protein interactions (PPIs) as well as novel PPIs predicted using our previously developed HiPPIP computational model and analysed it for transcriptomic and functional associations and for repurposable drugs.</p><h3 dir="ltr">Results</h3><p dir="ltr">The MPeM interactome had over 400 computationally predicted PPIs and 4700 known PPIs. Transcriptomic evidence validated 75.6% of the genes in the interactome and 65% of the novel interactors. Some genes had tissue-specific expression in extramedullary hematopoietic sites and the expression of some genes could be correlated with unfavourable prognoses in various cancers. 39 out of 152 drugs that target the proteins in the interactome were identified as potentially repurposable for MPeM, with 29 having evidence from prior clinical trials, animal models or cell lines for effectiveness against peritoneal and pleural mesothelioma and primary peritoneal cancer. Functional modules related to chromosomal segregation, transcriptional dysregulation, IL-6 production and hematopoiesis were identified from the interactome. The MPeM interactome overlapped significantly with the malignant pleural mesothelioma interactome, revealing shared molecular pathways.</p><h3 dir="ltr">Conclusions</h3><p dir="ltr">Our findings demonstrate the utility of the interactome in uncovering biological associations and in generating clinically translatable results.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: BJC Reports<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/10.1038/s44276-024-00062-w" target="_blank">https://dx.doi.org/10.1038/s44276-024-00062-w</a></p>2024-05-24T15:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1038/s44276-024-00062-whttps://figshare.com/articles/journal_contribution/Malignant_peritoneal_mesothelioma_interactome_with_417_novel_protein_protein_interactions/31444096CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/314440962024-05-24T15:00:00Z |
| spellingShingle | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions Kalyani B. Karunakaran (12478431) Biological sciences Genetics Biomedical and clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Gene expression Transcriptomic Molecular pathways Drug repurposing cancer biology |
| status_str | publishedVersion |
| title | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| title_full | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| title_fullStr | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| title_full_unstemmed | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| title_short | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| title_sort | Malignant peritoneal mesothelioma interactome with 417 novel protein–protein interactions |
| topic | Biological sciences Genetics Biomedical and clinical sciences Oncology and carcinogenesis Pharmacology and pharmaceutical sciences Gene expression Transcriptomic Molecular pathways Drug repurposing cancer biology |