Abstract 3448: ERG-negative index tumor status combined with obesity predict prostate cancer progression in Caucasian American prostate cancer patients

Author(s):  
Jennifer Cullen ◽  
Denise Young ◽  
Yongmei Chen ◽  
Michael S. Degon ◽  
Wagner Baptiste ◽  
...  
Cancers ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 239 ◽  
Author(s):  
I Ruma ◽  
Rie Kinoshita ◽  
Nahoko Tomonobu ◽  
Yusuke Inoue ◽  
Eisaku Kondo ◽  
...  

Embigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is involved in prostate and mammary gland development. As embigin’s roles in cancer remain elusive, we studied its biological functions and interaction with extracellular S100A4 in prostate cancer progression. We found by a pull-down assay that embigin is a novel receptor for S100A4, which is one of the vital cancer microenvironment milleu. Binding of extracellular S100A4 to embigin mediates prostate cancer progression by inhibition of AMPK activity, activation of NF-κB, MMP9 and mTORC1 signaling, and inhibition of autophagy, which increase prostate cancer cell motility. We also found that embigin promotes prostate cancer growth, spheroid- and colony-forming ability, and survival upon chemotherapy independently of S100A4. An in vivo growth mouse model confirmed the importance of embigin and its cytoplasmic tail in mediating prostate tumor growth. Moreover, embigin and p21WAF1 can be used to predict survival of prostate cancer patients. Our results demonstrated for the first time that the S100A4-embigin/AMPK/mTORC1/p21WAF1 and NF-κB/MMP9 axis is a vital oncogenic molecular cascade for prostate cancer progression. We proposed that embigin and p21WAF1 could be used as prognostic biomarkers and a strategy to inhibit S100A4-embigin binding could be a therapeutic approach for prostate cancer patients.


2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 44-44
Author(s):  
M. Kohli ◽  
D. W. Mahoney ◽  
H. S. Chai ◽  
D. W. Hillman ◽  
D. R. Rider ◽  
...  

44 Background: We investigated the association of germline genetic variation in hormone biosynthesis and metabolism genes with prostate cancer specific mortality in a cohort of advanced prostate cancer patients. Methods: We successfully genotyped 852 single nucleotide polymorphisms (SNPs) from 97 genes in a cohort of 267 advanced prostate cancer patients at the time of progression to castration recurrence (CRPC) during on-going androgen ablation. Tagging SNPs with minor allele frequency (MAF) of >5% and r2 ≥0.8 were selected from HapMap, NIEHS and Seattle SNP databases. Medical records were queried for cause of death. The primary endpoint of time to prostate cancer specific mortality (PCSM), was pre-defined as time from development of CRPC to death from prostate cancer progression. Principle components analysis was used for gene-levels tests, and to account for multiple testing, we calculated the false discovery rate (FDR). For SNP level results, hazard ratios (HR) and 95% confidence intervals (CI) were estimated using cox regression. Results: The median age of the cohort was 72 years at CRPC. 43% had a Gleason score (GS)=8-10, 33% a GS=7, and 24% a GS<7. After a median follow-up of 1.8 years (IQ range: 0.8–3.3 years), 139 patients died, of which 107 were due to prostate cancer progression. In unadjusted gene level analyses, UGT1A7 (p=0.0059; FDR=0.19), UGT1A10 (p=0.0017; FDR=0.17) and UGT1A3 (p=0.0037; FDR=0.18) were associated with PCSM. After adjusting for age and GS, SNPs strongly associated with PCSM are listed in the Table . Conclusions: Variation in UGT genes involved in hormone metabolism yield prognostic information in CRPC. Further validation is needed to develop these as prognostic biomarkers. [Table: see text] No significant financial relationships to disclose.


2009 ◽  
Vol 27 (19) ◽  
pp. 3161-3168 ◽  
Author(s):  
Lorenzo Richiardi ◽  
Valentina Fiano ◽  
Loredana Vizzini ◽  
Laura De Marco ◽  
Luisa Delsedime ◽  
...  

Purpose There is a need to better understand prostate cancer progression and identify new prognostic markers for this tumor. We investigated the association between promoter methylation in a priori selected genes and survival in two independent large series of prostate cancer patients. Methods We followed up with two cohorts of patients (216 patients diagnosed in 1982 to 1988 and 243 patients diagnosed in 1993 to 1996) diagnosed at one hospital pathology ward in Turin, Italy. DNA was obtained from paraffin-embedded tumor tissues and evaluated for promoter methylation status in glutathione S-transferase (GSTP1), adenomatous polyposis coli (APC), and runt-related transcription factor 3 (RUNX3). Results The two cohorts had different prevalences of methylation in APC (P = .047), GSTP1 (P = .002), and RUNX3 (P < .001). Methylation in APC was associated with an increased risk of prostate cancer–specific mortality (hazard ratio [HR] = 1.42; 95% CI, 0.98 to 2.07 in the 1980s cohort; HR = 1.57; 95% CI, 0.95 to 2.62 in the 1990s cohort; HR = 1.49; 95% CI, 1.11 to 2.00 in the two cohorts combined). In subgroup analyses, the HRs were higher among patients with a Gleason score less than 8 (HR = 1.52; 95% CI, 0.85 to 2.73 in the 1980s cohort; HR = 2.09; 95% CI, 1.02 to 4.28 in the 1990s cohort). Methylation in RUNX3 was associated with prostate cancer mortality only in the 1990s cohort, and methylation in GSTP1 did not predict mortality in either cohort. Conclusion The pattern of hypermethylation may have changed after the introduction of prostate-specific antigen testing in the beginning of the 1990s. Promoter methylation in APC was identified as a marker for prostate cancer progression.


Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1346
Author(s):  
Chien-Chih Ke ◽  
Lih-Chyang Chen ◽  
Chia-Cheng Yu ◽  
Wei-Chung Cheng ◽  
Chao-Yuan Huang ◽  
...  

The genes that influence prostate cancer progression remain largely unknown. Since the carboxylesterase gene family plays a crucial role in xenobiotic metabolism and lipid/cholesterol homeostasis, we hypothesize that genetic variants in carboxylesterase genes may influence clinical outcomes for prostate cancer patients. A total of 478 (36 genotyped and 442 imputed) single nucleotide polymorphisms (SNPs) in five genes of the carboxylesterase family were assessed in terms of their associations with biochemical recurrence (BCR)-free survival in 643 Taiwanese patients with prostate cancer who underwent radical prostatectomy. The strongest association signal was shown in CES1 (P = 9.64 × 10−4 for genotyped SNP rs8192935 and P = 8.96 × 10−5 for imputed SNP rs8192950). After multiple test correction and adjustment for clinical covariates, CES1 rs8192935 (P = 9.67 × 10−4) and rs8192950 (P = 9.34 × 10−5) remained significant. These SNPs were correlated with CES1 expression levels, which in turn were associated with prostate cancer aggressiveness. Furthermore, our meta-analysis, including eight studies, indicated that a high CES1 expression predicted better outcomes among prostate cancer patients (hazard ratio 0.82, 95% confidence interval 0.70–0.97, P = 0.02). In conclusion, our findings suggest that CES1 rs8192935 and rs8192950 are associated with BCR and that CES1 plays a tumor suppressive role in prostate cancer.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Takashi Kawahara ◽  
Masashi Kato ◽  
Kenichi Tabata ◽  
Ippei Kojima ◽  
Hiroshi Yamada ◽  
...  

Abstract Background Inflammatory cytokine markers, including the neutrophil-to-lymphocyte ratio (NLR), monocyte-lymphocyte ratio, and platelet-to-lymphocyte ratio, play important roles as prognostic markers in several solid malignancies, including prostate cancer. We previously reported the NLR as a poor prognostic marker in bladder cancer, upper-urothelial carcinoma, adrenocortical carcinoma, penile cancer, and prostate cancer. This study examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received abiraterone acetate or enzalutamide. Methods A total of 805 prostate cancer patients developed in CRPC status were enrolled in this study. Of these patients, 449 received abiraterone acetate (ABI; 188 cases) or enzalutamide (ENZ; 261 cases) treatment, and the pre-treatment NLR values of these patients were obtained. We investigated the prognosis in those with higher and lower NLR values. Results The median NLR was 2.90, and a receiver operating characteristics analysis suggested a candidate cut-off point of 3.02. The median overall survival (OS) was 17.3 months in the higher NLR group (≥3.02) and 27.3 months in the lower NLR group (< 3.02) (p < 0.0001). This trend was also observed in both the ABI and ENZ groups (ABI: 29.3 vs. 15.1 months; ENZ: NR vs. 19.5 months; p < 0.0001 and < 0.0001, respectively). A multivariate analysis revealed that a higher NLR was an independent risk factor. The NLR value was thus shown to be correlated with the prostate cancer progression. Conclusions A higher NLR was associated with a poorer OS for CRPC patients who received ABI or ENZ. The NLR was positively correlated with prostate cancer progression.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4646-4646
Author(s):  
Namratha R Vontela ◽  
Robert B Lane ◽  
Csaba Kovesdy ◽  
Alva Weir

Abstract INTRODUCTION: Idiopathic thrombocytopenic purpura (ITP) is a common autoimmune disorder. The association between ITP and lymphoid neoplasms is well known, but the association of ITP with solid tumors is poorly documented. To date only one case of prostate cancer associated with ITP has been reported in the literature and the association was unclear. The purpose of this study is to estimate the incidence of ITP in men with prostate cancer and to characterize its clinical course. METHODS: We performed a retrospective cohort study using a large multi-institutional database of 3,258,677 US veterans to identify those with and without prostate cancer (ICD-9 code 185). We evaluated them during the years 2006-2011 for the development of ITP using ICD-9 code 287.31. We examined the association of the presence of prostate cancer with incident ITP using Cox proportional hazard analyses, with adjustments for age, race, and presence of systemic lupus erythematosus, lymphomas and rheumatoid arthritis. In order to increase the specificity and sensitivity of our evaluation and to analyze the characteristics associated with ITP in prostate cancer, we then evaluated patients visiting the Memphis Veterans Administration Medical Center (VAMC) between January 2006 and December 2011. We identified 3973 patients with prostate cancer and randomly selected 4801 patients without prostate cancer during the same time period. In both of these cohorts, we performed an in depth chart review of all the patients with thrombocytopenic disorders, expanding the ICD.9 codes to 287.31 (ITP) and 287.5 (Thrombocytopenia NOS). We identified patients with ITP based on the American Society of Hematology criteria for the diagnosis. We then reviewed the ITP identified charts for characteristics of disease. RESULTS: Among 3,258,677 US veterans without a baseline diagnosis of thrombocytopenia, we identified 265,446 patients with prostate cancer and 2,993,231 patients without prostate cancer. In both these cohorts 1,847 patients developed ITP according to ICD.9 code 287.31. The incidence of ITP in patients with prostate cancer was 12.3/100,000 patient years (95%CI: 10.7-14.2) and in patients without prostate cancer was 9.5/100,000 patient years (95% CL: 9.0-10.0). Prostate cancer was associated with a 30% higher risk of incident ITP in unadjusted analyses (hazard ratio, 95%CI: 1.30, 1.12-1.51, p=0.001), but the difference was non-significant after multivariable adjustments (adjusted HR, 95%CI: 1.11, 0.95-1.30, p=0.18). Men with prostate cancer were older than controls (mean age 69 vs 59). Patients with ITP were more likely to have lupus (2.0% vs. 0.2%), lymphomas (7.3% vs. 0.8%) and rheumatoid arthritis (3.6% vs. 1.8%).This analysis provided a broad correlation between ITP and prostate cancer but lacked sensitivity due to the specificity of the single ICD-9 code. In our chart review of 3973 veterans with prostate cancer, we identified six cases of ITP (30/100,000 patient years). Among 4801 veterans without prostate cancer, none developed ITP. These numbers were too small to demonstrate clinical significance. The prostate cancer patients in our local institution were older than the controls (67.6 vs 57.7), similar to the age discrepancy in the large VA database. In none of the patients with ITP, thrombocytopenia was attributable to prior irradiation or chemotherapy. Two patients had severe ITP episodes preceding prostate cancer progression. Four patients had ITP worsening with stable prostate cancer and one patient had stable ITP with prostate cancer progression. Two of the ITP patients never required treatment, three required and responded to steroids and immunosuppressive drugs, and of these one required splenectomy. CONCLUSION: ITP, identified by the ICD-9 code 287.31 in a large multi-institutional survey, occurs more often in patients with prostate cancer, but this association may be due to confounding variables such as age. The true incidence is likely higher than this. At the Memphis VAMC, utilizing broader ICD.9 codes, including both ITP and Thrombocytopenia NOS, followed by an in-depth chart review, there is a strong suggestion of an increased incidence of ITP among prostate cancer patients, but the numbers are too small to be clinically significant. The clinical course of ITP in prostate cancer patients is similar to that seen with other disorders and does not clearly parallel the course of the prostate cancer. Disclosures No relevant conflicts of interest to declare.


2005 ◽  
Vol 173 (4S) ◽  
pp. 126-127
Author(s):  
Yingming Li ◽  
Melissa Thompson ◽  
Zhu Chen ◽  
Bahaa S. Malaeb ◽  
David Corey ◽  
...  

2006 ◽  
Vol 175 (4S) ◽  
pp. 155-156
Author(s):  
Matthias D. Hofer ◽  
Sven Perner ◽  
Haojie Li ◽  
Rainer Kuefer ◽  
Richard E. Hautmann ◽  
...  

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