MRS measured fatty acid composition of periprostatic adipose tissue correlates with pathological measures of prostate cancer aggressiveness

Iordanescu, Gheorghe; Brendler, Charles B.; Crawford, Susan E.; Wyrwicz, Alice M.; Venkatasubramanian, Palamadai N.; Doll, Jennifer A.

doi:10.1002/jmri.24824

Cited by 18 publications

(25 citation statements)

References 38 publications

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“…One of our hypotheses focused on PPAT due to previous in vitro research that showed that coculture with PPAT produced an aggressive phenotype in prostate cancer cells 28,29 . One study used magnetic resonance spectroscopy and found that the fatty acid composition was altered in PPAT of patients with aggressive prostate cancer 30 . When observing secretions from PPAT explants, PPAT‐conditioned media from more obese patients caused significantly more proliferation of prostate cancer and endothelial cells in vitro than PPAT‐conditioned media obtained from leaner men 31 .…”

Section: Discussionmentioning

confidence: 99%

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy

et al. 2020

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Background Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI. Materials and Methods We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation‐treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable‐adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT). Results Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow‐up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87‐3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24‐1.03; P‐interaction = .002), though neither association reached statistical significance. Similar patterns of ADT‐stratified associations were observed for PPAT and SFA. Conclusions Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.

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Section: Discussionmentioning

confidence: 99%

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy

et al. 2020

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“…In addition to the potential for enhanced fatty acid release and transfer to PCa cells, the composition of fatty acids in the PPAT is commonly altered in PCa compared to benign prostatic tissue . For example, Quiroga et al.…”

Section: Potential Mechanistic Links Between Peri‐prostatic Adipose Tmentioning

confidence: 99%

“…Similarly, Iordanescu et al. used magnetic resonance spectroscopy to show that PPAT from patients with more aggressive PCa has a higher ratio of monounsaturated/saturated fatty acids. However, this relationship was not observed with high Gleason scores (7 vs 6), which may be attributable in part to those patients with Gleason score 7 being a mixed population of 4 + 3 (only four patients) and 3 + 4 (13 patients).…”

Section: Potential Mechanistic Links Between Peri‐prostatic Adipose Tmentioning

confidence: 99%

Peri‐prostatic adipose tissue: the metabolic microenvironment of prostate cancer

et al. 2018

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Emerging data have linked certain features of clinical prostate cancer (PCa) to obesity and, more specifically, increased adiposity. Whereas the large number of clinical studies and meta-analyses that have explored the associations between PCa and obesity have shown considerable variability, particularly in relation to prostate cancer risk, there is an accumulating weight of evidence consistently linking obesity to greater aggressiveness of disease. In probing this association mechanistically, it has been posited that peri-prostatic adipose tissue (PPAT), a significant component of the prostate microenvironment, may be a critical source of fatty acids and other mitogens and thereby influences PCa pathogenesis and progression. Notably, several recent studies have identified secreted factors from both PPAT and PCa that potentially mediate the two-way communication between these intimately linked tissues. In the present review, we summarize the available literature regarding the relationship between PPAT and PCa, including the potential biological mediators of that relationship, and explore emerging areas of interest for future research endeavours.

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“…Periprostatic adipose tissue (PPAT), a white fat depot surrounding the prostate capsular-like structure, has been recognized to have the potential to exert pro-tumoral endocrine and paracrine influences on prostate cancer cell’s biological phenotypes [ 4 ]. There is now evidence that obesity and overweight result in excess fat deposit at PPAT [ 5 ], altered fatty acid profile [ 6 ], migration of tumor cells [ 7 ], secretion of a variety of adipokines, such as interleukin-1 beta (IL-1b), osteopontin, leptin, tumor necrosis factor alpha (TNF-a), and decreased adiponectin, thus contributing to a tumor microenvironment that ultimately facilitates PCa aggressiveness [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study

et al. 2018

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BackgroundPeriprostatic adipose tissue (PPAT) has been recognized to associate with prostate cancer (PCa) aggressiveness and progression. Here, we sought to investigate whether excess adiposity modulates the methylome of PPAT in PCa patients. DNA methylation profiling was performed in PPAT from obese/overweight (OB/OW, BMI > 25 kg m−2) and normal weight (NW, BMI < 25 kg m−2) PCa patients. Significant differences in methylated CpGs between OB/OW and NW groups were inferred by statistical modeling.ResultsFive thousand five hundred twenty-six differentially methylated CpGs were identified between OB/OW and NW PCa patients with 90.2% hypermethylated. Four hundred eighty-three of these CpGs were found to be located at both promoters and CpG islands, whereas the representing 412 genes were found to be involved in pluripotency of stem cells, fatty acid metabolism, and many other biological processes; 14 of these genes, particularly FADS1, MOGAT1, and PCYT2, with promoter hypermethylation presented with significantly decreased gene expression in matched samples. Additionally, 38 genes were correlated with antigen processing and presentation of endogenous antigen via MHC class I, which might result in fatty acid accumulation in PPAT and tumor immune evasion.ConclusionsResults showed that the whole epigenome methylation profiles of PPAT were significantly different in OB/OW compared to normal weight PCa patients. The epigenetic variation associated with excess adiposity likely resulted in altered lipid metabolism and immune dysregulation, contributing towards unfavorable PCa microenvironment, thus warranting further validation studies in larger samples.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0490-3) contains supplementary material, which is available to authorized users.

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MRS measured fatty acid composition of periprostatic adipose tissue correlates with pathological measures of prostate cancer aggressiveness

Abstract: Fatty acid composition is altered in the PPA tissue of patients with aggressive prostate cancer. Ex vivo MR spectroscopy may be a useful tool in studying the altered fatty acid metabolism in prostate cancer.

Cited by 18 publications

References 38 publications

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy

Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy

Peri‐prostatic adipose tissue: the metabolic microenvironment of prostate cancer

Epigenome-wide DNA methylation profiling of periprostatic adipose tissue in prostate cancer patients with excess adiposity—a pilot study

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