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Ossoliński et al. J Cancer Metastasis Treat 2019;5:1 I http://dx.doi.org/10.20517/2394-4722.2018.63 Page 9 of 12

Elevated serum cholesterol and triglycerides (TG) has been linked with increased risk of developing
aggressive PCa and recurrence after radical prostatectomy [33-36] . However there is discrepancy between
studies concerning association between serum lipids level and overall risk of developing PCa [37-39] .

[40]
Eberlin et al. showed that cholesterol sulfate (CS) which is the product of cholesterol sulfotransferase -
SULT2B1 (within cells cholesterol occurs in form of esters, CS or hydroxycholesterol), accumulates in PCa
and achieves higher concentration in comparison to benign prostate tissue. However, in our study, levels of
CS in biofluids of cancer patients have not been elevated. Moreover, in comparison to control, a statistically
significant decrease of intensity in urine has been observed (P < 0.05).

Another interesting aspect of affinity of PCa cells to adipose-rich environment is fact that most common
metastatic sites are lymph nodes and bone marrow. This environment provides sufficient TG which are
hydrolyzed to fatty acids to fuel mitochondrial beta-oxidation and ATP generation [28,41] . This observation
initiated research of new generation of drugs that target lipid metabolism [28,42] . In this study increased
intensity of TG in urine of PCa patients has been observed.

[43]
Fatty acids transport inside mitochondria is possible by its conjugation to carnitine. Giskeødegård et al.
reported elevated serum level of four acyl carnitines in PCa patients in comparison to benign prostatic
[44]
hyperplasia (BPH) control and Saylor et al. observed decrease in serum acyl carnitines concentration
after 3 months of androgen deprivation therapy. In comparison, no acyl carnitines was elevated in our study,
moreover, serum nonanoylcarnitine intensity of PCa patients was decreased in comparison to control (P = 0.05).

One of the most studied dietary-factor related with PCa risk is daily intake of omega-3 fatty acids, however
results are still inconsistent. Only alpha-linolenic acid (ALA) out of all n-3 polyunsaturated fatty acids (ALA,
eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid) is essential (cannot be synthesized
in the body and must be obtained from food). Recent meta-analysis showed only marginally significant
negative association between PCa risk and intake of ALA and no significant association between ALA blood
[45]
concentration and PCa risk . In this study serum ALA intensity was statistically significant lower in patients
with PCa in comparison to control (P < 0.05).

Relationship between vitamin D (and its active metabolite - calcitriol) intake and its serum level and risk
of PCa has been broadly studied. Vitamin D deficiency is associated with increased odds of PCa on biopsy
and it is positively associated with higher PCa grade and stage [46,47] . Moreover, calcitriol used alone or as a
part of combination therapy is being studied in clinical trials to treat PCa [48-50] . This is explained by the effect
of vitamin D in promoting cellular apoptosis and differentiation and inhibiting cancer proliferation and
angiogenesis. By decreasing expression of COX-2 gene it reduces proliferative stimulus of prostaglandin,
a COX-2 product [51,52] . Our study supports observation that serum vitamin D deficiency is relevant in
pathogenesis of PCa.

Another interesting observation is higher abundance of vitamin C metabolites in the serum of patients with
PCa. Relationship between daily intake of vitamin C and risk of developing PCa is highly debatable and
the results are conflicting. Its antineoplastic properties are attributed to its antioxidative properties which
protects DNA and RNA from oxidative damage. However at high doses it may act as a pro-oxidant rather
[53]
than antioxidant . In our study elevated serum concentration of vitamin C metabolites in serum of patients
with PCa has been observed.

The proliferative state of carcinoma requires both amino acids and nucleic acids to fuel cell division. We
observed increased level of different amino acids in serum and simultaneously its decreased level in urine