IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms
Introduction: IQGAP3 possesses oncogenic actions; its impact on prostate cancer (PC) remains unclear. Objective: We will investigate IQGAP3′s association with PC progression, key mechanisms, prognosis, and immune evasion. Methods: IQGAP3 expression in PC was examined by immunohistochemistry and usin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Journal of Advanced Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123223000280 |
| _version_ | 1827620813637943296 |
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| author | Wenjuan Mei Ying Dong Yan Gu Anil Kapoor Xiaozeng Lin Yingying Su Sandra Vega Neira Damu Tang |
| author_facet | Wenjuan Mei Ying Dong Yan Gu Anil Kapoor Xiaozeng Lin Yingying Su Sandra Vega Neira Damu Tang |
| author_sort | Wenjuan Mei |
| collection | DOAJ |
| description | Introduction: IQGAP3 possesses oncogenic actions; its impact on prostate cancer (PC) remains unclear. Objective: We will investigate IQGAP3′s association with PC progression, key mechanisms, prognosis, and immune evasion. Methods: IQGAP3 expression in PC was examined by immunohistochemistry and using multiple datasets. IQGAP3 network was analyzed for pathway alterations and used to construct a multigene signature (SigIQGAP3NW). SigIQGAP3NW was characterized using LNCaP cell-derived castration-resistant PCs (CRPCs), analyzed for prognostic value in 26 human cancer types, and studied for association with immune evasion. Results: Increases in IQGAP3 expression associated with PC tumorigenesis, tumor grade, metastasis, and p53 mutation. IQGAP3 correlative genes were dominantly involved in mitosis. IQGAP3 correlated with PLK1 and TOP2A expression at Spearman correlation/R = 0.89 (p ≤ 3.069e-169). Both correlations were enriched in advanced PCs and Taxane-treated CRPCs and occurred at high levels (R > 0.8) in multiple cancer types. SigIQGAP3NW effectively predicted cancer recurrence and poor prognosis in independent PC cohorts and across 26 cancer types. SigIQGAP3NW stratified PC recurrence after adjustment for age at diagnosis, grade, stage, and surgical margin. SigIQGAP3NW component genes were upregulated in PC, metastasis, LNCaP cell-produced CRPC, and showed an association with p53 mutation. SigIQGAP3NW correlated with immune cell infiltration, including Treg in PC and other cancers. RELT, a SigIQGAP3NW component gene, was associated with elevations of multiple immune checkpoints and the infiltration of Treg and myeloid-derived suppressor cells in PC and across cancer types. RELT and SigIQGAP3NW predict response to immune checkpoint blockade (ICB) therapy. Conclusions: In multiple cancers, IQGAP3 robustly correlates with PLK1 and TOP2A expression, and SigIQGAP3NW and/or RELT effectively predict mortality risk and/or resistance to ICB therapy. PLK1 and TOP2A inhibitors should be investigated for treating cancers with elevated IQGAP3 expression. SigIQGAP3NW and/or RELT can be developed for clinical applications in risk stratification and management of ICB therapy. |
| first_indexed | 2024-03-09T10:53:15Z |
| format | Article |
| id | doaj.art-485ac59ffab84301b40eadee2d3799ec |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-03-09T10:53:15Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
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| series | Journal of Advanced Research |
| spelling | doaj.art-485ac59ffab84301b40eadee2d3799ec2023-12-01T05:01:21ZengElsevierJournal of Advanced Research2090-12322023-12-0154195210IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanismsWenjuan Mei0Ying Dong1Yan Gu2Anil Kapoor3Xiaozeng Lin4Yingying Su5Sandra Vega Neira6Damu Tang7Department of Nephrology, The First Affiliated Hospital of Nanchang University, Jiangxi, China; Urological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Corresponding authors at: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China (W. Mei). T3310, St. Joseph’s Hospital, 50 Charlton Ave East, Hamilton, ON L8N 4A6, Canada (D. Tang).Urological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, CanadaUrological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, CanadaUrological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, CanadaUrological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, CanadaUrological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, CanadaUrological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, CanadaUrological Cancer Center for Research and Innovation (UCCRI), St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Department of Surgery, McMaster University, Hamilton, ON L8S 4K1, Canada; The Research Institute of St Joe’s Hamilton, St Joseph’s Hospital, Hamilton, ON L8N 4A6, Canada; Corresponding authors at: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China (W. Mei). T3310, St. Joseph’s Hospital, 50 Charlton Ave East, Hamilton, ON L8N 4A6, Canada (D. Tang).Introduction: IQGAP3 possesses oncogenic actions; its impact on prostate cancer (PC) remains unclear. Objective: We will investigate IQGAP3′s association with PC progression, key mechanisms, prognosis, and immune evasion. Methods: IQGAP3 expression in PC was examined by immunohistochemistry and using multiple datasets. IQGAP3 network was analyzed for pathway alterations and used to construct a multigene signature (SigIQGAP3NW). SigIQGAP3NW was characterized using LNCaP cell-derived castration-resistant PCs (CRPCs), analyzed for prognostic value in 26 human cancer types, and studied for association with immune evasion. Results: Increases in IQGAP3 expression associated with PC tumorigenesis, tumor grade, metastasis, and p53 mutation. IQGAP3 correlative genes were dominantly involved in mitosis. IQGAP3 correlated with PLK1 and TOP2A expression at Spearman correlation/R = 0.89 (p ≤ 3.069e-169). Both correlations were enriched in advanced PCs and Taxane-treated CRPCs and occurred at high levels (R > 0.8) in multiple cancer types. SigIQGAP3NW effectively predicted cancer recurrence and poor prognosis in independent PC cohorts and across 26 cancer types. SigIQGAP3NW stratified PC recurrence after adjustment for age at diagnosis, grade, stage, and surgical margin. SigIQGAP3NW component genes were upregulated in PC, metastasis, LNCaP cell-produced CRPC, and showed an association with p53 mutation. SigIQGAP3NW correlated with immune cell infiltration, including Treg in PC and other cancers. RELT, a SigIQGAP3NW component gene, was associated with elevations of multiple immune checkpoints and the infiltration of Treg and myeloid-derived suppressor cells in PC and across cancer types. RELT and SigIQGAP3NW predict response to immune checkpoint blockade (ICB) therapy. Conclusions: In multiple cancers, IQGAP3 robustly correlates with PLK1 and TOP2A expression, and SigIQGAP3NW and/or RELT effectively predict mortality risk and/or resistance to ICB therapy. PLK1 and TOP2A inhibitors should be investigated for treating cancers with elevated IQGAP3 expression. SigIQGAP3NW and/or RELT can be developed for clinical applications in risk stratification and management of ICB therapy.http://www.sciencedirect.com/science/article/pii/S2090123223000280IQGAP3Prostate cancerClinical relevancePrognostic predictionOverall survivalImmune checkpoint blockade therapy |
| spellingShingle | Wenjuan Mei Ying Dong Yan Gu Anil Kapoor Xiaozeng Lin Yingying Su Sandra Vega Neira Damu Tang IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms Journal of Advanced Research IQGAP3 Prostate cancer Clinical relevance Prognostic prediction Overall survival Immune checkpoint blockade therapy |
| title | IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms |
| title_full | IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms |
| title_fullStr | IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms |
| title_full_unstemmed | IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms |
| title_short | IQGAP3 is relevant to prostate cancer: A detailed presentation of potential pathomechanisms |
| title_sort | iqgap3 is relevant to prostate cancer a detailed presentation of potential pathomechanisms |
| topic | IQGAP3 Prostate cancer Clinical relevance Prognostic prediction Overall survival Immune checkpoint blockade therapy |
| url | http://www.sciencedirect.com/science/article/pii/S2090123223000280 |
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