Serum and Saliva Concentrations of Biochemical Parameters in Men With Prostate Cancer and Benign Prostate Hyperplasia

Hyder Farahani, PhD; Mona Alaee, MSc; Jamal Amri, MSc; Mahmoud-Reza Baghinia, MD; Mohammad Rafiee, PhD

Disclosures

Lab Med. 2020;51(3):243-251. 

In This Article

Abstract and Introduction

Abstract

Objectives: To find suitable biomarkers for diagnosis of prostate cancer (PC) in serum and saliva; also, to evaluate the diagnostic efficacy of saliva in patients with PC.

Methods: This case-control study included 20 patients with PC and 20 patients with benign prostatic hyperplasia (BPH). Blood and saliva were collected from the participants and centrifuged. Serum and supernatant saliva were used for biochemical analysis. We evaluated serum and salivary levels of urea, creatinine, prostate-specific antigen (PSA), creatine kinase BB (CK-BB), zinc, β-2 microglobulin (B2M), and melatonin. Also, we used Mann-Whitney U testing, Spearman correlation coefficients, and receiver operating characteristic (ROC) analysis to evaluate the data.

Results: Serum and salivary concentrations of urea, creatinine, PSA, CK-BB, zinc, and B2M were significantly higher in patients with PC, compared with the BPH group (P <.05). However, serum and salivary concentrations of melatonin were significantly lower in patients with PC, compared with BPH group (P <.05). In both groups, salivary concentrations of all markers were lower (P <.05), compared with those values in serum. We observed positive correlation between serum and salivary concentrations of all markers studied (P <.05).

Conclusion: From the data, we conclude that investigation using saliva specimens is a noninvasive, simple, and effective tool for screening of biochemical parameters.

Introduction

Prostate cancer is the most common malignant neoplasm in males and the 6th-most-prevalent cause of cancer mortality worldwide.[1] Because patients with cancer are often diagnosed in the advanced stages of the disease, it is necessary to identify novel methods for early detection.[2] Use of saliva, a clear liquid that is essential for oral health and possesses several biological functions,[3] as a specimen has been described in the literature[4] as being a noninvasive, safe, and cost-effective procedure that can be applied to large populations. According to the results of a recent meta-analysis,[5] several groups have reported that changes in the concentrations of salivary components are associated with different diseases.

The purpose of this study was to examine the relationship between serum and salivary concentrations of certain biochemical markers and to compare them among patients with prostate cancer (PC) and patients with benign prostatic hyperplasia (BPH). Use of prostate-specific antigen (PSA) measurements in the diagnosis of PC is a controversial issue.[3] Therefore, in this study, we aimed to find an appropriate biomarker for early detection and evaluation of saliva as a biological specimen.

PSA, or human kallikrein-3, is a glycoprotein that is abundantly expressed in the healthy epithelial cells of the prostate gland.[7] PSA screening is associated with disadvantages, including incorrect diagnoses (false-negative or false-positive results), overdiagnosis, and overtreatment.[8] Although high concentrations of PSA can indicate PC, PSA levels may also increase in conditions such as BPH or during/after prostate manipulation.[9]

Melatonin (MT) is the main product of the pineal gland in humans.[10] MT rapidly enters the bloodstream and then spreads to other body fluids, including saliva.[11] In addition to systemic functions such as maintaining circadian rhythms, MT also reduces cellular proliferation and decreases cell death at the cellular level.[12] Recent observations, such as those by Jung-Hynes et al,[13] have shown that reducing the production of MT leads to disturbed circadian rhythms and increases the risk of cancer.

Beta-2 microglobulin (B2M), a major histocompatibility complex (MHC) class I subunit, is a low-molecular-weight protein (11/8 kDa) that contains 100 amino acids.[14] Aberrant expression of MHC I in patients with PC has been reported.[15] This protein is found in serum and other body fluids; its concentration increases in renal failure and some malignant neoplasms.[14] In normal physiological conditions, a certain amount of B2M may enter the bloodstream from cell surfaces or as a result of intracellular release and is mainly removed by the kidneys. Therefore, in people without kidney disease, elevated B2M concentration can be considered a marker of changes in cell proliferation.[16]

Creatine kinase (CK) is an enzyme expressed by various cells that plays a central role in energy transfer in tissues;[17] the role of CK in cell-cycle regulation has turned it into a diagnostic biomarker.[18] The results of 2 studies related to CK concentrations[19,20] are contradictory. Other researchers[21] observed upregulated expression of CK-BB, a cytosolic isoform of CK, in a variety of cancers. The results of a previous study[19] have shown that the expression of creatine kinase BB (CK-BB) leads to increased proliferation and secretion of cytokines from T-cells. Therefore, low concentrations of CK can reflect a weak status of the immune response and thus lead to the progression of cancer.

Zinc is an essential nutrient that is involved in many physiological processes.[22] The prostate, as a zinc-accumulating organ, contains a higher level of zinc than many other tissues.[23] It has been observed[22] that zinc induces apoptosis and sensitizes malignant cells to apoptosis. Also, healthy prostate cells can store a large amount of zinc, whereas malignant cells are associated with a significant decrease in zinc concentrations.

Renal dysfunction is common in patients with newly diagnosed cancer.[24] Creatinine is an excreted material that results in the metabolism of creatine phosphate in the muscle. Creatinine excreted in the kidney via glomerular filtration. It is a measure a biomarker of renal injury.[25] Serum creatinine has been reported[26] to be associated with an increased risk of PC, especially in advanced stages. Urea is the most central final product of protein catabolism in the liver.[27] The concentration of urea in serum is one of the most frequently determined clinical indices for estimating renal function. Joshi et al[28] report that elevation of urea concentration can be a primary indicator for PC.

Using saliva for diagnosis is noninvasive; saliva is more easily accessible than other biological fluids. Therefore, it is necessary to standardize the use of saliva for the measurement of various parameters in clinical laboratories. In fact, utilizing specific tumor markers can lead to early detection of cancer. Therefore, in this article, we report the results of our research regarding whether it is possible to assess the relationship between salivary and serum PSA, B2M, CK-BB, MT, zinc, creatinine, and urea levels in PC and BPH groups.

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