Association between Expression of Connective Tissue Genes and Prostate Cancer Growth and Progression
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Published:2023-04-19
Issue:8
Volume:24
Page:7520
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Treacy Patrick-Julien12, Martini Alberto13, Falagario Ugo Giovanni14, Ratnani Parita1, Wajswol Ethan1, Beksac Alp Tuna1, Wiklund Peter1, Nair Sujit1ORCID, Kyprianou Natasha15ORCID, Durand Matthieu2, Tewari Ashutosh K.1
Affiliation:
1. Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA 2. Department of Urology and Organ Transplantation, Nice University Hospital, 06003 Nice, France 3. Department of Urology, Vita-Salute San Raffaele University, 20132 Milan, Italy 4. Department of Urology and Organ Transplantation, University of Foggia, 71122 Foggia, Italy 5. Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Abstract
To find an association between genomic features of connective tissue and pejorative clinical outcomes on radical prostatectomy specimens. We performed a retrospective analysis of patients who underwent radical prostatectomy and underwent a Decipher transcriptomic test for localized prostate cancer in our institution (n = 695). The expression results of selected connective tissue genes were analyzed after multiple t tests, revealing significant differences in the transcriptomic expression (over- or under-expression). We investigated the association between transcript results and clinical features such as extra-capsular extension (ECE), clinically significant cancer, lymph node (LN) invasion and early biochemical recurrence (eBCR), defined as earlier than 3 years after surgery). The Cancer Genome Atlas (TCGA) was used to evaluate the prognostic role of genes on progression-free survival (PFS) and overall survival (OS). Out of 528 patients, we found that 189 had ECE and 27 had LN invasion. The Decipher score was higher in patients with ECE, LN invasion, and eBCR. Our gene selection microarray analysis showed an overexpression in both ECE and LN invasion, and in clinically significant cancer for COL1A1, COL1A2, COL3A1, LUM, VCAN, FN1, AEBP1, ASPN, TIMP1, TIMP3, BGN, and underexpression in FMOD and FLNA. In the TCGA population, overexpression of these genes was correlated with worse PFS. Significant co-occurrence of these genes was observed. When presenting overexpression of our gene selection, the 5-year PFS rate was 53% vs. 68% (p = 0.0315). Transcriptomic overexpression of connective tissue genes correlated to worse clinical features, such as ECE, clinically significant cancer and BCR, identifying the potential prognostic value of the gene signature of the connective tissue in prostate cancer. TCGAp cohort analysis showed a worse PFS in case of overexpression of the connective tissue genes.
Funder
French Association “Les Amis de la Faculté de Nice”
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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