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Volume 25
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10.3390/ijms25168913
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Article

Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer

by
Mutlay Sayan
1,*,
Yetkin Tuac
2,
Mahmut Akgul
3,
Samet Kucukcolak
4,
Elza Tjio
5,
Dilara Akbulut
6,
Luke W. Chen
1,
David D. Yang
1,
Shalini Moningi
1,
Jonathan E. Leeman
1,
Peter F. Orio
1,
Paul L. Nguyen
1,
Anthony V. D’Amico
1 and
Cagdas Aktan
7
1
Department of Radiation Oncology, Brigham and Women’s Hospital and Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA
2
Department of Statistics, Ankara University, Ankara 06100, Türkiye
3
Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, USA
4
Department of Pathology and Laboratory Medicine, Rutgers University, New Brunswick, NJ 07102, USA
5
Histopathology Department, Harrogate District Hospital, Harrogate HG2 7SX, UK
6
Laboratory of Pathology, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA
7
Department of Medical Biology, Faculty of Medicine, Bandirma Onyedi Eylul University, Balikesir 10250, Türkiye
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(16), 8913; https://doi.org/10.3390/ijms25168913
Submission received: 29 June 2024 / Revised: 13 August 2024 / Accepted: 13 August 2024 / Published: 16 August 2024
(This article belongs to the Special Issue Advances in Prostate Cancer Diagnostics and Therapy)
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Abstract

Prostate cancer has substantial heterogeneity in clinical outcomes and therapeutic responses, posing challenges in predicting disease progression and tailoring treatment strategies. Recent studies have highlighted the potential prognostic value of evaluating the tumor microenvironment, including the presence of a histologically overt stromal response (HOST-response) characterized by peri-glandular stromal changes and architectural distortions. This retrospective study examined patient records from The Cancer Genome Atlas database to identify genomic alterations associated with the HOST-response in prostate cancer. Among 348 patients who underwent radical prostatectomy, 160 (45.98%) were identified as having a HOST-response. A gene expression analysis revealed 1263 genes with significantly higher expression in patients with a HOST-response. A protein–protein interaction network analysis identified seven hub genes (KIF2C, CENPA, CDC20, UBE2C, ESPL1, KIF23, and PLK1) highly interconnected in the network. A functional enrichment analysis revealed alterations in the cell division, cytoskeletal organization, cytokinesis, and interleukin-16 signaling pathways in patients with a HOST-response, suggesting dysregulated proliferation and inflammation. The distinct molecular signature associated with the HOST-response provides insights into the tumor–stroma interactions driving adverse outcomes and potential targets for tailored therapeutic interventions in this subset of patients with prostate cancer.
Keywords: prostate cancer; HOST-response; genomic instability; tumor microenvironment prostate cancer; HOST-response; genomic instability; tumor microenvironment

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MDPI and ACS Style

Sayan, M.; Tuac, Y.; Akgul, M.; Kucukcolak, S.; Tjio, E.; Akbulut, D.; Chen, L.W.; Yang, D.D.; Moningi, S.; Leeman, J.E.; et al. Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer. Int. J. Mol. Sci. 2024, 25, 8913. https://doi.org/10.3390/ijms25168913

AMA Style

Sayan M, Tuac Y, Akgul M, Kucukcolak S, Tjio E, Akbulut D, Chen LW, Yang DD, Moningi S, Leeman JE, et al. Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer. International Journal of Molecular Sciences. 2024; 25(16):8913. https://doi.org/10.3390/ijms25168913

Chicago/Turabian Style

Sayan, Mutlay, Yetkin Tuac, Mahmut Akgul, Samet Kucukcolak, Elza Tjio, Dilara Akbulut, Luke W. Chen, David D. Yang, Shalini Moningi, Jonathan E. Leeman, and et al. 2024. "Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer" International Journal of Molecular Sciences 25, no. 16: 8913. https://doi.org/10.3390/ijms25168913

APA Style

Sayan, M., Tuac, Y., Akgul, M., Kucukcolak, S., Tjio, E., Akbulut, D., Chen, L. W., Yang, D. D., Moningi, S., Leeman, J. E., Orio, P. F., Nguyen, P. L., D’Amico, A. V., & Aktan, C. (2024). Molecular Alterations Associated with Histologically Overt Stromal Response in Patients with Prostate Cancer. International Journal of Molecular Sciences, 25(16), 8913. https://doi.org/10.3390/ijms25168913

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