Molecular Changes in Tissue Proteome during Prostate Cancer Development: Proof-of-Principle Investigation

(1) Background: Prostate cancer (PCa) is characterized by high heterogeneity. The aim of this study was to investigate molecular alterations underlying PCa development based on proteomics data. (2) Methods: Liquid chromatography coupled to tandem mass spectrometry was conducted for 22 fresh-frozen tissue specimens from patients with benign prostatic hyperplasia (BPH, n = 5) and PCa (n = 17). Mann Whitney test was used to define significant differences between the two groups. Association of protein abundance with PCa progression was evaluated using Spearman correlation, followed by verification through investigating the Prostate Cancer Transcriptome Atlas. Functional enrichment and interactome analysis were carried out using Metascape and String. (3) Results: Proteomics analysis identified 1433 proteins, including 145 proteins as differentially abundant between patients with PCa and BPH. In silico analysis revealed alterations in several pathways and hallmarks implicated in metabolism and signalling, represented by 67 proteins. Among the latter, 21 proteins were correlated with PCa progression at both the protein and mRNA levels. Interactome analysis of these 21 proteins predicted interactions between Myc proto-oncogene (MYC) targets, protein processing in the endoplasmic reticulum, and oxidative phosphorylation, with MYC targets having a central role. (4) Conclusions: Tissue proteomics allowed for characterization of proteins and pathways consistently affected during PCa development. Further validation of these findings is required.

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MMP-9 Overexpression Due to TIMP-1 and RECK Underexpression is Associated with Prognosis in Prostate Cancer

The International Journal of Biological Markers ◽

10.5301/jbm.2011.8831 ◽

2011 ◽

Vol 26 (4) ◽

pp. 255-261 ◽

Cited By ~ 15

Author(s):

Sabrina Thalita Reis ◽

José Pontes-Junior ◽

Alberto Azoubel Antunes ◽

Juliana Moreira De Sousa-Canavez ◽

Marcos Francisco Dall'Oglio ◽

...

Keyword(s):

Prostate Cancer ◽

Statistical Significance ◽

Specific Pattern ◽

Control Group ◽

Negative Regulators ◽

Prostate Hyperplasia ◽

Fresh Frozen ◽

Polymerase Chain ◽

Tissue Specimens

Background Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their inhibitors. The purpose of this study was to investigate whether the expression of MMP-9 and its specific inhibitors, TIMP-1 and RECK, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome in prostate cancer (PC). Methods MMP-9, TIMP-1, and RECK expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in fresh-frozen malignant tissue specimens collected from 79 patients with clinically localized PC submitted to radical prostatectomy (RP). Frozen benign prostatic tissue from another 10 men with prostate cancer, also submitted to RP, was analyzed to determine if the profile of gene expression was maintained. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). Results In the tumor samples, MMP-9 was overexpressed by 9.2 times, and TIMP-1 and RECK were underexpressed (0.75 and 0.80 times, respectively). Overexpression of MMP-9 was significantly related to PSA levels above 10 ng/mL (p=0.033). In addition, MMP-9 overexpression was related to biochemical recurrence, with a marginal statistical significance (p=0.089). MMP-9 was also overexpressed in benign tissues of patients with PC, as were TIMP-1 and RECK, in contrast to their underexpression in tumor samples. Conclusion Our results show that MMP-9 is overexpressed and its negative regulators are underexpressed in PC tissue, emphasizing a possible role of MMP-9 in the carcinogenesis process. Additionally, we noticed a relationship between MMP-9 overexpression and increased levels of PSA, an important prognostic factor. In benign tissue adjacent to tumors, the MMP-9 equilibrium is likely maintained because the expression of its negative regulators is preserved.

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Molecular alterations associated with prostate cancer development

Molecular Biology of Prostate Cancer ◽

10.1515/9783110807271.53 ◽

2013 ◽

Author(s):

M. J. G. Bussemakers ◽

J. A. Schalken

Keyword(s):

Prostate Cancer ◽

Cancer Development ◽

Molecular Alterations ◽

Prostate Cancer Development

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N-Linked Glycosylation and Near-Infrared Spectroscopy in the Diagnosis of Prostate Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20071592 ◽

2019 ◽

Vol 20 (7) ◽

pp. 1592

Author(s):

Tijl Vermassen ◽

Sander De Bruyne ◽

Jonas Himpe ◽

Nicolaas Lumen ◽

Nico Callewaert ◽

...

Keyword(s):

Prostate Cancer ◽

Infrared Spectroscopy ◽

Near Infrared Spectroscopy ◽

Near Infrared ◽

Nir Spectroscopy ◽

Prostate Tissue ◽

Malignant Tissue ◽

Prostate Hyperplasia ◽

Fresh Frozen ◽

Tissue Specimens

Background: Performing a prostate biopsy is the most robust and reliable way to diagnose prostate cancer (PCa), and to determine the disease grading. As little to no biochemical markers for prostate tissue exist, we explored the possibilities of tissue N-glycosylation and near-infrared spectroscopy (NIR) in PCa diagnosis. Methods: Tissue specimens from 100 patients (benign prostate hyperplasia (BPH), n = 50; and PCa, n = 50) were obtained. The fresh-frozen tissue was dispersed and a tissue N-glycosylation profile was determined. Consequently, the formalin-fixed paraffin-embedded slides were analyzed using NIR spectroscopy. A comparison was made between the benign and malignant tissue, and between the various Gleason scores. Results: A difference was observed for the tissue of N-glycosylation between the benign and malignant tissue. These differences were located in the fycosylation ratios and the total amount of bi- and tetra-antennary structures (all p < 0.0001). These differences were also present between various Gleason scores. In addition, the NIR spectra revealed changes between the benign and malignant tissue in several regions. Moreover, spectral ranges of 1055–1065 nm and 1450–1460 nm were significantly different between the Gleason scores (p = 0.0042 and p = 0.0195). Conclusions: We have demonstrated biochemical changes in the N-glycan profile of prostate tissue, which allows for the distinction between malignant and benign tissue, as well as between various Gleason scores. These changes can be correlated to the changes observed in the NIR spectra. This could possibly further improve the histological assessment of PCa diagnosis, although further method validation is needed.

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