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Sequencing Small Non-coding RNA from Formalin-fixed Tissues and Serum-derived Exosomes from Castration-resistant Prostate Cancer Patients
Published on: November 19, 2019
Epigenetic silencing of SOCS3 identifies a subset of prostate cancer with an aggressive behavior
Francesco Pierconti1, Maurizio Martini, Francesco Pinto
1Institute of Pathological Anatomy, Catholic University of Sacred Heart, Rome, Italy.
Background:
Chronic inflammation and subsequent tissutal alterations may play a key role in prostate carcinogenesis. In this way, molecular alterations of the suppressor of cytokine signaling 3 (SOCS3), one of the most important inhibitory molecule of inflammatory signal transduction circuitries, could contribute to explain the pleiotropic role of interleukin-6 (IL-6) in this type of cancer.
Methods:
We analyzed the methylation status and mRNA expression of SOCS3 in 20 benign prostate hyperplasias (BPH) and in 51 prostate cancer specimens. We analyzed the SOCS3 methylation status using methylation-specific PCR. Hypermethylation was confirmed by sequencing after subcloning. Epigenetic silencing of this gene was also demonstrated by real-time PCR and by immunohistochemistry. Results and correlation with clinical data were statistically analyzed.
Results:
We found that the promoter of SOCS3 was methylated in 39.2% of prostate cancer. On the contrary, all BPH and normal controls had an unmethylated pattern. Real-time analysis showed that in methylated cases SOCS3 mRNA expression was reduced by three and four folds as compared to BPH and unmethylated cases, respectively. Interestingly, SOCS3 mRNA level was higher in unmethylated prostate cancer than in BPH. The immunohistochemical staining analysis for SOCS 3 confirmed mRNA results. Moreover, methylation of SOCS3 promoter significantly associated with intermediate-high grade Gleason score (P = 0.0007) and with an unfavorable clinical outcome (P = 0.0019).
Conclusions:
Our data suggest that SOCS3 hypermethylation may be involved in the pathogenesis of prostate cancer and could identify a tumor subset with an aggressive behavior.
Insights
Suppressor of cytokine signaling 3 (SOCS3) gene promoter hypermethylation is frequent in prostate cancer, leading to reduced expression and association with aggressive disease. This epigenetic silencing may drive prostate cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Chronic inflammation and tissue alterations are implicated in prostate cancer development.
- The suppressor of cytokine signaling 3 (SOCS3) gene regulates inflammatory signaling pathways, particularly involving interleukin-6 (IL-6).
- Alterations in SOCS3 may contribute to the complex role of IL-6 in prostate carcinogenesis.
Purpose of the Study:
- To investigate the methylation status and mRNA expression of the SOCS3 gene in benign prostate hyperplasia (BPH) and prostate cancer.
- To determine the correlation between SOCS3 epigenetic alterations and clinical parameters in prostate cancer patients.
Main Methods:
- Analysis of SOCS3 promoter methylation using methylation-specific PCR and sequencing.
- Quantification of SOCS3 mRNA expression via real-time PCR.
- Assessment of SOCS3 protein levels through immunohistochemistry.
- Statistical analysis of results and clinical data.
Main Results:
- SOCS3 promoter hypermethylation was detected in 39.2% of prostate cancer specimens, but not in BPH or normal controls.
- Methylated SOCS3 cases exhibited significantly reduced mRNA expression compared to BPH and unmethylated prostate cancer.
- SOCS3 promoter methylation strongly correlated with higher Gleason scores and unfavorable clinical outcomes in prostate cancer.
Conclusions:
- SOCS3 hypermethylation is a potential mechanism involved in prostate cancer pathogenesis.
- Epigenetic silencing of SOCS3 may identify a subset of prostate tumors with aggressive behavior.
- SOCS3 alterations represent a potential biomarker for predicting prostate cancer prognosis.
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