Citric Acid as a Potential Prostate Cancer Biomarker Determined in Various Biological Samples

Abstract

Despite numerous studies, the molecular mechanism of prostate cancer development is still unknown. Recent investigations indicated that citric acid and lipids—with a special emphasis on fatty acids, steroids and hormones (ex. prolactin)—play a significant role in prostate cancer development and progression. However, citric acid is assumed to be a potential biomarker of prostate cancer, due to which, the diagnosis at an early stage of the disease could be possible. For this reason, the main goal of this study is to determine the citric acid concentration in three different matrices. To the best of our knowledge, this is the first time for citric acid to be determined in three different matrices (tissue, urine and blood). Samples were collected from patients diagnosed with prostate cancer and from a selected control group (individuals with benign prostatic hyperplasia). The analyses were performed using the rapid fluorometric test. The obtained results were correlated with both the histopathological data (the Gleason scale as well as the Classification of Malignant Tumors (pTNM) staging scale) and the biochemical data (the values of the following factors: prostate specific antigen, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, total cholesterol, creatinine and prolactin) using chemometric methods. For tissue samples, the results indicated a decreased level of citric acid in the case of prostate cancer. The analyte average concentrations in serum and urine appeared to be corresponding and superior in the positive cohort. This trend was statistically significant in the case of urinary citric acid. Moreover, a significant negative correlation was demonstrated between the concentration of citric acid and the tumor stage. A negative correlation between the total cholesterol and high-density lipoprotein and prolactin was particularly prominent in cancer cases. Conversely, a negative association between low-density lipoprotein and prolactin levels was observed solely in the control group. On the basis of the results, one may assume the influence of hormones, particularly prolactin, on the development of prostate cancer. The present research allowed us to verify the possibility of using citric acid as a potential biomarker for prostate cancer.

Integrative Metabolomic Analysis of Serum and Selected Serum Exosomal microRNA in Metastatic Castration-Resistant Prostate Cancer

“…We hypothesize that PC cells take up this serum citrate through specific transporters expressed in the plasma membrane [ 34 , 35 ], and intracellularly utilize it to support PC metabolism, proliferation, fatty acid synthesis, and protein acetylation [ 36 ]. Similar findings were reported by Buszewska-Forajta et al (2022), who observed higher serum concentrations of citrate in a PC group compared to a BPH group, with no significant changes in citrate concentration based on the clinical stage of the tumor [ 37 ]. In contrast, Kumar et al (2016) reported a significant decrease in citrate levels in filtered serum obtained from PC patients compared to BPH patients [ 32 ].…”

Circulating metabolites as potential biomarkers for the early detection and prognosis surveillance of gastrointestinal cancers

“…As speculated, citric acid was significantly elevated in CRC samples (Amir Hashim et al, 2021 ; Tan et al, 2013 ; Uchiyama et al, 2017 ; Zamani et al, 2014 ). Besides, Buszewska-Forajta et al, found that citric acid was changed in prostate patient and have significant correlations with tumor progression (Buszewska-Forajta et al, 2022 ). In our study, the citric acid concentration was decreased after surgical resection, which is logical with the previous finding.…”

Differentiation of patients with and without prostate cancer using urine 1H NMR metabolomics

“…15 Increased citrate oxidation is frequently observed in malignant cells, resulting in decreased citrate levels in prostatic and seminal fluid in PCa groups. 16 Since citrate can be converted to lactate via the intermediates oxaloacetate and pyruvate, decreased citrate levels could lead to decreased conversion to lactate, which accounts for the observed decreased lactate. Nonetheless, our results that indicate the alteration of lactate in PCa suggests changes in cellular energy metabolism during cancer development.…”

“…However, malignant prostatic tissue is unable to accumulate zinc, resulting in increased citrate oxidation and TCA cycle activity 15 . Increased citrate oxidation is frequently observed in malignant cells, resulting in decreased citrate levels in prostatic and seminal fluid in PCa groups 16 . Since citrate can be converted to lactate via the intermediates oxaloacetate and pyruvate, decreased citrate levels could lead to decreased conversion to lactate, which accounts for the observed decreased lactate.…”