A Preliminary Study of Tumor Microenvironment Interleukin-4 as Promoter in Immune Escape Event in Prostate Cancer

Introduction : This study aims to investigate the relationship between IL-4 expression with Apoptosis-associated gene receptors (PD-1, CTLA-4) and Programmed Death-1 Ligands (PD-L1, PD-L2) in the microenvironment of prostate cancer tissue.Methods : The samples were collected from single-center hospital in a period from 2014 to 2020. Deparaffinize formalin-fixed paraffin-embedded and RNAs extraction by manufacturer’s protocol with slight modification was performed. The RNAs expressions were investigated by using quantitative real-time polymerase chain reaction. Then we categorize them into 4 groups. The ANOVA test is used to compare mean expression between groups and followed by a correlation test using Pearson test.Result : In the BPH group sample, CTLA-4 had the highest expression level, followed by the expression of IL-4, PD-L2, then PD-1 and PD-L1. The concentration of IL-4 in prostate cancer, both metastatic and non-metastatic, is higher than in BPH, with a p-value of 0.006. the correlation between IL-4 and PD-L1 is the strongest (r=0.919), between IL-4 and PD-L2 comes the second (0.832) and between PD-1 is comes the third (r=0.626).Conclusion : In this study, we find that the expression of IL-4 and Apoptosis-Associated Gene Receptors (PD-1, CTLA-4) and Programmed Death-1 Ligands (PD-L1, PD-L2) in the prostate cancer tissue microenvironment have a significant relationship. In conclusion, it is possible that IL-4 is a promoter of the Immune Escape mechanism in prostate cancer.

Why not to use punch biopsies in formalin-fixed paraffin-embedded samples of prostate cancer tissue for DNA and RNA extraction?

Extraction of DNA and RNA from formalin-fixed paraffin-embedded (FFPE) tissue blocks is a critical process in molecular oncology testing. Using FFPE, it is possible to choose the portion of tissue to study, taking into account the cell morphology, storage stability and storage conditions at room temperature, and make retrospective studies with clinical and pathological information. In prostate cancer tissue, in contrast with macroscopic tumors, it is not easy to identify the tumor; therefore, it is very important to make a microscopic diagnosis. We do not recommend punching this tissue because it can choose normal tissue for molecular analysis. In the present article we review the differences between punch biopsy and microdissection.

Androgen receptor splice variant 7 detected by immunohistochemical is an independent poor prognostic marker in men receiving adjuvant androgen-deprivation therapy after radical prostatectomy

Background To evaluate the predictive value of AR-V7 expression detected by immunohistochemical (IHC) in the prognosis of prostate cancer patients receiving adjuvant hormonal therapy (AHT) following radical prostatectomy (RP). Methods We retrospectively collected data of 110 patients with prostate cancer receiving RP, followed by AHT, from Tongji hospital. IHC analysis of AR-V7 expression was performed in a retrospective cohort. Results In total, 110 patients were enrolled, of whom 21 patients (19.1%) were AR-V7-positive and 89 patients (80.9%) were AR-V7-negative. No significant differences in baseline characteristics were found between the two groups. AR-V7-positive patients had shorter progression-free survival (PFS) (HR: 4.26; 95% CI, 1.55 to 11.68; P = 0.003), shorter cancer-special survival (CSS) (HR: 22.47; 95% CI, 2.912 to 173.4; P = 0.003) and shorter overall survival (OS) (HR: 6.61; 95% CI, 1.40 to 31.20; P = 0.017) compared to AR-V7-negative patients. In multivariate analysis, AR-V7 is an independent risk factor for shorter PFS (HR, 3.76; 95% CI, 1.63 to 8.70; P = 0.002), shorter CSS (HR: 9.17; 95% CI, 1.48 to 55.56; P = 0.017) and shorter OS (HR: 4.81; 95% CI, 1.28 to 17.86; P = 0.020). Conclusion The presence of AR-V7 in prostate cancer tissue is independently associated with an unfavorable prognosis for PFS, OS and CSS in patients who received AHT.

Comprehensive genomic profiling of matched primary prostate cancer tissue and cell-free DNA (cfDNA) to assess ontogeny of BRCA1/BRCA2 mutations.

166 Background: Both olaparib and rucaparib have recently been approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) with BRCA1/2 mutations (BRCAm). In the PROFOUND trial, 36.9% of men had either no tissue or tissue that was inadequate for genomic profiling (PMID: 32343890). A recent report suggests BRCAm may be an early event in the evolution of prostate cancer (PMID: 29662167). This suggests comprehensive genomic profiling (CGP) of primary prostate tissue may suffice to guide treatment selection, even years after tissue collection. Herein, we investigate the ontogeny of BRCAm by comparing CGP of matched primary prostate cancer tissue to CGP of cfDNA. Methods: Eligibility criteria included men diagnosed with metastatic prostate cancer that had matched CGP of both primary prostate cancer tissue and cfDNA. Genomic profiling was performed by CLIA certified laboratories. Only somatic mutations detectable by both platforms were used for concordance analysis. Results: We identified 198 patients that had matched CGP of primary prostate tissue and cfDNA. Thirteen men had a pathogenic BRCAm in at least one test. Of these 13 positive test for BRCAm, 2 were rearrangements, 1 copy number loss, and 5 were germline mutations. Both platforms tend to filter out germline alterations therefore, they were not included in the estimation of concordance. Overall somatic BRCAm concordance between primary prostate tissue and cfDNA was 196/198 (98%). Notably, no new BRCAm were identified in cfDNA with a median difference of 23.62 (0.1 - 232.2) months between prostate cancer tissue and cfDNA collection. Conclusions: There were no BRCAm detected only in cfDNA, suggesting that BRCAm is an early event in the ontogeny of prostate cancer. Based on this, it is unlikely that delaying sequencing would benefit patients with advanced prostate cancer. In the event that tissue is unavailable or inadequate for CGP, profiling of cfDNA is a valuable alternative for detection of BRCAm.

Clinical significance of STEAP1 extracellular vesicles in prostate cancer

Background Extracellular vesicles (EVs) are cell-derived lipid bilayer enclosed structures shed from the plasma membrane by all cell types. Evidence of EV presence in biological fluids has led to considerable efforts focused on identifying their cargo and determining their utility as a non-invasive diagnostic platform for cancer. In this study, we identify circulating STEAP1 (six-transmembrane epithelial antigen of the prostate 1)-positive EVs in the plasma of healthy males and prostate cancer patients and evaluate its diagnostic and prognostic significance. Methods STEAP1 was identified on EVs in prostate cancer patient plasma. EVs were validated using electron microscopy, Western blot, nanoparticle tracking analysis, and nanoscale flow cytometry. STEAP1-positive EVs were quantified for 121 males with prostate cancer and 55 healthy age-matched control males. An evaluation of STEAP1 in prostate cancer tissue was also performed using established prostate cancer cohort data (TCGA, MSKCC, and SU2C/PCF Dream Team). Results Evaluation of STEAP1-positive EVs by nanoscale flow cytometry identified a significant increase in prostate cancer patient plasma compared to healthy males. However, no association was found between total STEAP1 EV levels and disease recurrence or overall survival. Cohort data from prostate cancer tissue also found STEAP1 to be elevated in prostate cancer while no significant association with recurrence or overall survival was identified. Conclusions STEAP1 is known to be enriched on the cells of the prostate with potential clinical significance in prostate cancer. Our results identify and quantitate STEAP1-positive EVs in plasma and provide rationale for a STEAP1 EV-based liquid biopsy as a diagnostic strategy in prostate cancer.