scholarly journals Lipid Alterations in African American Prostate Cancer

2021 ◽  
Author(s):  
Anindita Ravindran ◽  
Danthasinghe Waduge Badrajee Piyarathna ◽  
Jie Gohlke ◽  
Vasanta Putluri ◽  
Tanu Soni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Biochemical Recurrence ◽  
In Silico Analysis ◽  
Cholesteryl Esters ◽  
Entire Cohort ◽  
Polyunsaturated Lipids ◽  
Pan Cancer ◽  
Silico Analysis ◽  
Altered Lipid

African-American (AA) men are more than twice as likely to die of prostate cancer (PCa) than European American (EA) men. Previous in-silico analysis revealed enrichment of altered lipid metabolic pathways in pan-cancer AA tumors. Here, we performed global unbiased lipidomics profiling on 48 matched localized PCa and benign adjacent tissues (30 AA, 24 ancestry-verified, and 18 EA, 8 ancestry verified) and quantified 429 lipids belonging to 15 lipid classes. Significant alterations in long chain polyunsaturated lipids was observed between PCa and benign adjacent tissues, low and high Gleason tumors, as well as associated with early biochemical recurrence, both in the entire cohort, and within AA patients. Altered levels of cholesteryl esters, and phosphatidyl inositols delineated AA and EA PCa, while levels of triglycerides, phosphatidyl glycerol, phosphatidyl choline, phosphatidic acid and cholesteryl esters distinguished AA and EA PCa patients with biochemical recurrence. These first-in-field results implicate lipid alterations as biological factors for prostate cancer disparities.

scholarly journals Lipid Alterations in African American Men with Prostate Cancer

Metabolites ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 8
Author(s):  
Anindita Ravindran ◽  
Danthasinghe Waduge Badrajee Piyarathna ◽  
Jie Gohlke ◽  
Vasanta Putluri ◽  
Tanu Soni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Biochemical Recurrence ◽  
African American Men ◽  
Phosphatidyl Inositol ◽  
In Silico Analysis ◽  
Cholesteryl Esters ◽  
Entire Cohort ◽  
Polyunsaturated Lipids ◽  
Altered Lipid

African-American (AA) men are more than twice as likely to die of prostate cancer (PCa) than European American (EA) men. Previous in silico analysis revealed enrichment of altered lipid metabolic pathways in pan-cancer AA tumors. Here, we performed global unbiased lipidomics profiling on 48 matched localized PCa and benign adjacent tissues (30 AA, 24 ancestry-verified, and 18 EA, 8 ancestry verified) and quantified 429 lipids belonging to 14 lipid classes. Significant alterations in long chain polyunsaturated lipids were observed between PCa and benign adjacent tissues, low and high Gleason tumors, as well as associated with early biochemical recurrence, both in the entire cohort, and within AA patients. Alterations in cholesteryl esters, and phosphatidyl inositol classes of lipids delineated AA and EA PCa, while the levels of lipids belonging to triglycerides, phosphatidyl glycerol, phosphatidyl choline, phosphatidic acid, and cholesteryl esters distinguished AA and EA PCa patients with biochemical recurrence. These first-in-field results implicate lipid alterations as biological factors for prostate cancer disparities.

In silico analysis of non-synonymous single nucleotide polymorphism in a human KLK-2 gene associated with prostate cancer

Meta Gene ◽  
2019 ◽  
Vol 21 ◽  
pp. 100578
Author(s):  
Tooba Yousefi ◽  
Seyed Mostafa Mir ◽  
Jahanbakhsh Asadi ◽  
Mehdi Tourani ◽  
Ansar Karimian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Single Nucleotide Polymorphism ◽  
In Silico ◽  
In Silico Analysis ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Silico Analysis

In silico analysis and DHPLC screening strategy identifies novel apoptotic gene targets of aberrant promoter hypermethylation in prostate cancer

The Prostate ◽  
2010 ◽  
Vol 71 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Therese M. Murphy ◽  
Linda Sullivan ◽  
Caroline Lane ◽  
Lisa O'Connor ◽  
Ciara Barrett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
In Silico ◽  
In Silico Analysis ◽  
Promoter Hypermethylation ◽  
Screening Strategy ◽  
Apoptotic Gene ◽  
Silico Analysis

Genomic variations associated with prostate cancer in large cohort of African American men.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 20-20
Author(s):  
Rayford Walter ◽  
Jennifer Jordan ◽  
Mandeep Takhar ◽  
Mohammed Alshalalfa ◽  
Darlene Dai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Dna Repair ◽  
African American ◽  
Racial Disparities ◽  
African American Men ◽  
Race Model ◽  
Immune Infiltration ◽  
Incidence And Mortality ◽  
Pan Cancer

20 Background: Racial disparities in prostate cancer (PCa) incidence and mortality are well known. PCa is known to be more aggressive in African American men (AAM) in terms of higher incidence and mortality rates. Here we validate a tumor gene expression pan-cancer race model in men with PCa and further characterize genomic differences that may contribute to disparate clinical outcomes Methods: We obtained de-identified genome-wide expression profiles from clinical use of the Decipher RP test in 9,953 men from the GRID registry database. A subset of men (n = 313) had known race status. A pan-cancer race model, developed to predict patient AAM race from analysis of gene expression patterns in 4,162 tumors from retrospective cohorts with known race status was applied to the prospective cohort for race prediction. Gene expression data was used to define genomic differences. Results: The race model has an AUC of 0.98 discriminating EAM from AAM in independent PCa cohort. The model was then applied to the 9,640 GRID patients with unknown race status and classified 6,831 as EAM, 1,058 as AAM with 1,751 as having indeterminate race. Characterizing the molecular subtypes, we found known and predicted AAM to be enriched with SPINK1+ tumors (21% and 24%, respectively) compared to predicted EAM (8%). In contrast, while ERG+ was found 22% and 19% in known and predicted AAM, respectively compared to 46% in predicted EAM. Based on PAM50 prostate cancer classifier, 61% of AAM were classified as basal-like tumors, whereas 41% were basal-like in EAM. Similarly, 28% of AAM had low AR-A while only 11% of EAM had low AR-A. AAM tumors had higher levels of immune infiltration signatures as well as higher scores for inflammatory and interferon gamma responses, and Interleukin 6 (IL6) signaling activity scores. AAM had lower DNA repair and glycolysis pathway activity compared to EAM Conclusions: Known and predicted AAM, were enriched with SPINK1+ tumors, higher immune infiltration and activation but lower ERG+, DNA repair and AR activity tumors. Using such large GRID data with known race, we will further understand the underlying causes associated with prostate cancer racial disparities which could lead to personalized diagnosis and treatment.

Prostate cancer biochemical recurrence stage for stage is more frequent among African-American than white men with locally advanced but not organ-confined disease

Urology ◽  
2000 ◽  
Vol 55 (2) ◽  
pp. 246-251 ◽  
Author(s):  
Isaac J Powell ◽  
Mousumi Banerjee ◽  
Mary Novallo ◽  
Wael Sakr ◽  
David Grignon ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Biochemical Recurrence ◽  
Locally Advanced ◽  
White Men

Methylation of global DNA repeat LINE-1 and subtelomeric DNA repeats D4Z4 in leukocytes is associated with biochemical recurrence in African American prostate cancer patients

2019 ◽  
Vol 40 (9) ◽  
pp. 1055-1060
Author(s):  
Junfeng Xu ◽  
Chia-Wen Tsai ◽  
Wen-Shin Chang ◽  
Yuyan Han ◽  
Da-Tian Bau ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Methylation ◽  
African American ◽  
Confidence Interval ◽  
Biochemical Recurrence ◽  
Survival Function ◽  
Global Dna Methylation ◽  
Dna Repeats ◽  
Significant Difference ◽  
Epidemiological Characteristics

Abstract Global DNA methylation may play important roles in cancer etiology and prognosis. The goal of this study is to investigate whether the methylation of long interspersed nucleotide elements (LINE-1) and subtelomeric DNA repeats D4Z4 in leukocyte DNA is associated with aggressive prostate cancer (PCa) in African Americans. We measured DNA methylation levels of LINE-1 and D4Z4 in 306 African American (AA) PCa patients using pyrosequencing and compared their methylation levels among clinical variables. We further applied multivariate Cox proportional hazards model and Kaplan–Meier survival function and log-rank tests to assess the association between DNA methylation and biochemical recurrence (BCR). Overall, there was no significant difference of the methylation levels of LINE-1 and D4Z4 among patients with different clinical and epidemiological characteristics. However, the methylation of LINE-1 and D4Z4 was associated with BCR. Patients with lower LINE-1 methylation and higher D4Z4 methylation exhibited markedly increased risks of BCR with adjusted hazard ratios of 3.34 (95% confidence interval, 1.32–8.45) and 4.12 (95% confidence interval, 1.32–12.86), respectively, and significantly shorter BCR-free survival times. Our results suggest that lower global DNA methylation and higher subtelomeric region methylation may predict worse prognosis in localized AA PCa patients.

scholarly journals Proapoptosis Effect of Root of Eurycoma longifolia (Pasak Bumi) on the Prostate Cancer: In Silico Analysis

2020 ◽  
Vol 20 ◽  
pp. 03003
Author(s):  
Eka Yudha Rahman ◽  
Mulyohadi Ali ◽  
Basuki Bambang Purnomo ◽  
Nia Kania
Keyword(s):  
Prostate Cancer ◽  
In Silico ◽  
Caspase 3 ◽  
In Silico Analysis ◽  
Data Bank ◽  
Active Ingredients ◽  
Caspase 9 ◽  
Active Compounds ◽  
Eurycoma Longifolia ◽  
Silico Analysis

This study aimed to predict the proapoptosis effect of E. longifolia active compounds on prostate cancer by in silico analysis. Protein data such as BCL-2 (GI: 2506216), Caspase 3 (GI: 6978605), Caspase 8(GI: 11560103), data quassinoid (ID: 5459060 and chantin (ID: 97176) were collected from GenBank of NCBI. Protein BCL-2 collected from NCBI compare with Protein Data Bank (PDB) and UNIPROT. The docking process was carried out using software HEX 8.0. to compute the binding affinity between ligands (active compounds of Pasak Bumi) and protein target. The interaction between quassinoid and chantin was strongest and stable against caspase-9, indicating that the active ingredient in E. longifolia triggered caspase-9 activity after activation of BH3 domains in Bcl-2 in prostate cancer. The low energy binding between quassinoid and chantin with caspase-3 indicates the interaction between the active ingredients is not strong with caspase-3. E. longifolia active ingredients that are potentially used in the treatment of prostate cancer are quassinoid and chantin by inducing apoptotic mechanisms via both extrinsic and intrinsic pathways. The combination of active ingredients of E. longifolia that is quassinoid and chantin can be used as a strategy of prostate cancer therapy both through extrinsic and intrinsic pathways.

scholarly journals Pathologic and biochemical outcomes among African American and Caucasian men with low-risk prostate cancer in the search database: Implications for active surveillance candidacy.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 76-76
Author(s):  
Michael S. Leapman ◽  
Stephen J. Freedland ◽  
William J Aaronson ◽  
Christopher J. Kane ◽  
Martha K. Terris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Biochemical Recurrence ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Cox Proportional Hazards ◽  
Low Risk ◽  
Equal Access ◽  
Caucasian Race ◽  
Caucasian Men

76 Background: Racial disparities in the incidence and risk profile of prostate cancer (PCa) at diagnosis among African American (AA) men are well reported, however it remains unclear whether AA race is independently associated with adverse pathological findings among men with clinical low risk disease. Methods: We conducted a retrospective analysis among 895 men, with clinical low risk (Gleason 3+3, clinical stage ≤T2a, PSA≤10 ng/mL) treated with immediate radical prostatectomy within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We evaluated clinical and demographic characteristics by AA or Caucasian race. Associations between AA versus Caucasian race with pathologic Gleason upgrade (≥3+4), major upgrade (≥4+3), upstage (pT3a or higher), margin status and biochemical recurrence (BCR) were examined using chi-square, logistic regression, log-rank, and Cox proportional hazards analyses. Results: We identified 355 AA and 540 Caucasian men with low-risk tumors within the SEARCH cohort followed for a median of 6.3 (IQR 3.8-8.9). AA men were younger (mean 59.5vs. 62.0 years), and had higher median PSA (5.5 vs. 5.1). Following adjustment for relevant covariates, AA race was not significantly associated with pathological upgrade (OR 1.335, 95% CI 0.936-1.905, p=0.111), major upgrade (OR 0.561, 95% CI 0.300-1.049, p=0.070), upstaging (OR 1.111, 95% CI 0.670-1.844, p=0.683), or positive surgical margins (OR 1.046, 95% CI 0.732-1.494, p=0.806). The 5-year recurrence-free survival rates were 73.4% and 78.4% for AA and Caucasian men, respectively (log-rank p=0.178). After adjustment for clinical and pathological characteristics, AA race was not significantly associated with BCR (HR 1.1.054, 95% CI 0.814-1.501, p=0.521). Conclusions: In a cohort of low-risk men treated with prostatectomy within an equal access health system with a high representation of AA men, no significant differences were observed in the rates of pathologic upgrading, upstaging or biochemical recurrence. These data support continued use of AS in AA. Upgrading and upstaging remain concerning possibilities for all men regardless of race.

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