Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways

2021 ◽  
Author(s):  
Liu Yufei ◽  
Yang Chen ◽  
Zhang Zheyu ◽  
Jiang Haowen
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Repair Pathways ◽  
Gut Microbiota Dysbiosis

scholarly journals Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Yufei Liu ◽  
Chen Yang ◽  
Zheyu Zhang ◽  
Haowen Jiang
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Gut Microbiota ◽  
Cancer Progression ◽  
Fecal Microbiota Transplantation ◽  
Gene Set Enrichment Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Fecal Suspension ◽  
Repair Pathways ◽  
Gut Microbiota Dysbiosis

Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that Ruminococcus was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice’s prostate histopathology and gut microbiota composition were determined. Since Ruminococcus was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice’s fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut Ruminococcus was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice’s PCa progression and increased their gut Ruminococcus abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of Ruminococcus in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of Ruminococcus in PCa progression via upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.

Copy number variations in AR-associated and DNA repair genes from plasma cell-free DNA of metastatic CRPC patients.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
Ratish Gambhira ◽  
Elisa M. Ledet ◽  
Aryeneesh Dotiwala ◽  
Diptasri Mandal ◽  
A. Oliver Sartor
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Progression ◽  
Copy Number ◽  
Genetic Alterations ◽  
Copy Number Variations ◽  
Dna Repair Genes ◽  
Prostate Cancer Progression ◽  
Free Dna ◽  
Repair Genes

281 Background: Cell-free DNA (cfDNA) present in the plasma of advanced cancer patients can reflect tumor related genetic alterations. Recent data suggests copy number variations (CNVs) in AR-associated and DNA repair pathway genes play a potential role in prostate cancer progression. Here, we performed sequencing of cfDNA from 13 mCRPC patients to evaluate its potential in elucidating tumor related genetic variations. The long-term goal of our project is to correlate cfDNA derived genetic alterations with prostate cancer progression and/or therapeutic resistance/responses. Methods: cfDNA was isolated from 13 advanced mCRPC patient plasma samples using the Qiagen circulating nucleic acid kit. 100ng of cfDNA was utilized for library construction; and the libraries were paired-end sequenced on the Illumina HiSeq 2000. The resulting data was analyzed using the GATK best practices bioinformatics pipeline and the visualized using the SNP & Variation Suite v8.x. Results: The bioanalyzer profiles of cfDNA derived from mCRPC patients is highly fragmented with an average fragment size of 306-605bp. Although, several CNVs were found across the genome, we focused analysis on CNVs related to AR associated and DNA repair genes. Our preliminary analysis of cfDNA, despite low sequencing depth, shows full or partial amplifications in AR (13/13), and other genes including FOXA1, NCOR1, NCOR2 and/or PIK3CA (7/13) and NCOR2 (10/13). For DNA repair genes partial/full amplifications were present in BRAC1, BRAC2, ATM, CDK12, MLH1 and/or MSH2 (7/13). Deletions are less reliably detected in the highly fragmented cfDNA. The majority of these CNVs have been reported in the WGS studies from metastatic CRPC tissue derived genomic DNA (cBioPortal). We are currently validating cfDNA genomic alterations by comparing it to germ line DNA derived via qPCR. Conclusions: Our preliminary study indicates that AR and DNA repair related genetic alterations could be found in the cfDNA derived from metastatic CRPC patients. This warrants more detailed examination of these cfDNA genetic alterations for identifying clinically relevant issues in mCRPC patients.

scholarly journals Single nucleotide polymorphisms in DNA repair genes as risk factors associated to prostate cancer progression

2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Luis Alberto Henríquez-Hernández ◽  
Almudena Valenciano ◽  
Palmira Foro-Arnalot ◽  
María Jesús Álvarez-Cubero ◽  
José Manuel Cozar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Risk Factors ◽  
Dna Repair ◽  
Cancer Progression ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Prostate Cancer Progression ◽  
Single Nucleotide ◽  
Factors Associated ◽  
Repair Genes

scholarly journals Deficiency of DNA repair nuclease ERCC1-XPF promotes prostate cancer progression in a tissue recombination model

The Prostate ◽  
2011 ◽  
Vol 72 (11) ◽  
pp. 1214-1222 ◽  
Author(s):  
Derek J. Matoka ◽  
Veronica Yao ◽  
Diana S. Harya ◽  
Jennifer L. Gregg ◽  
Andria R. Robinson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Recombination Model ◽  
Tissue Recombination

DNA Repair System and Prostate Cancer Progression: The Role of NBS1 Polymorphism (rs1805794)

2012 ◽  
Vol 31 (7) ◽  
pp. 1182-1186 ◽  
Author(s):  
Joana Silva ◽  
Ana L. Teixeira ◽  
Francisco Lobo ◽  
Joaquina Maurício ◽  
Rui Medeiros
Keyword(s):  
Prostate Cancer ◽  
Dna Repair ◽  
Cancer Progression ◽  
Repair System ◽  
Prostate Cancer Progression

463: Telomerase Inhibition Prevents Androgen Independent Osseous Prostate Cancer Progression

2005 ◽  
Vol 173 (4S) ◽  
pp. 126-127
Author(s):  
Yingming Li ◽  
Melissa Thompson ◽  
Zhu Chen ◽  
Bahaa S. Malaeb ◽  
David Corey ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Cancer Progression ◽  
Telomerase Inhibition ◽  
Androgen Independent

479: Prostate-Specific Membrane Antigen (PSMA) Expression as a Predictor of Prostate Cancer Progression

2006 ◽  
Vol 175 (4S) ◽  
pp. 155-156
Author(s):  
Matthias D. Hofer ◽  
Sven Perner ◽  
Haojie Li ◽  
Rainer Kuefer ◽  
Richard E. Hautmann ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Prostate Specific Membrane Antigen ◽  
Prostate Cancer Progression ◽  
Specific Membrane ◽  
Psma Expression
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