Evaluation of Gamma-Glutamyl Transferase as a Diagnostic Biomarker for Prostate Cancer in Iraqi Patients

Prostate cancer (PCa) is the most common cancer affecting men, apart from cutaneous cancers. Serum prostate specific antigen (PSA) levels are frequently used to predict prostate cancer diagnosis. However, many causes (e.g., prostatitis, benign prostate obstruction, urethral catheterization) may cause elevated PSA, in addition to PCa. We aimed to investigate the gamma glutamyl transferase (GGT) levels, a serum biomarker not affected by situations other than cancer causing elevated PSA. The study evaluated male patients with prostate biopsy due to high serum PSA levels and/or abnormal digital rectal examination (DRE) examined in Ordu University Education and Research Hospital, Ordu/Turkey urology clinic from April 2019 to April 2021. The patient group in the study included 261 men with PCa diagnosis and the control group included 245 healthy men with normal PSA levels, and no PCa and/or benign prostate obstruction (BPO). The two groups were compared in terms of serum GGT levels. GGT was significantly low in the PCa group and might be a predictor in terms of PCa (P=0.000). In the malignant (PCa) group, the GGT cut-off value was identified as 21.5 (sensitivity 68.6%, specificity 54.4%). Serum GGT levels might assist in diagnosis of PCa. However, diagnostic power is weak due to low specificity. There is a need for studies investigating the efficacy of GGT levels for prediction of PCa diagnosis and assessing other parameters alongside GGT.

Increasing evidence indicates that inflammation may play important roles in tumorigenesis and progression, and an elevated peripheral monocyte count predicts a poor prognosis in various types of malignancies. Here, we evaluate the roles of peripheral monocyte count in the diagnosis and prognosis for prostate cancer in Chinese patients. A total of 1107 consecutive patients who had undergone prostate biopsy and 290 prostate cancer patients receiving androgen deprivation therapy as first-line therapy were retrospectively analyzed. The parameters were measured at the time of diagnosis. Univariate and multivariate logistic regression analyses were performed to identify the independent predictors of a positive biopsy. Patients were categorized in two groups using a cutoff point of 0.425 × 109 l−1 as calculated by the receiver-operating curve analysis for prognosis. Univariate and multivariate Cox regression analyses were performed to determine the associations of monocyte count with progression-free survival, cancer-specific survival, and overall survival. Multivariate logistic regression analyses showed that monocyte count, age, prostate-specific antigen (PSA), free/total PSA, and prostate volume were independent predictors for prostate cancer. Multivariate Cox regression analyses identified an elevated monocyte count as an independent prognostic factor for worse cancer-specific survival (hazard ratio = 2.244, P < 0.05) and overall survival (hazard ratio = 1.995, P < 0.05), but not progression-free survival (P = 0.117). Our results indicated that an elevated monocyte count was an independent diagnostic biomarker for prostate cancer, and pretreatment peripheral monocyte count might play a significant role in the prognosis of prostate cancer patients treated with androgen deprivation therapy.

With more than 230,000 new cases each year in the United States, prostate cancer is the most common cancer diagnosed among American men [(1)][1] . Prostate cancer is expected to account for nearly 30,000 deaths in the United States in 2004 and consequently represents the second most common cause of

Spondin-2, a Secreted Extracellular Matrix Protein, is a Novel Diagnostic Biomarker for Prostate Cancer

Urinary exosomal FAM153C-RPL19 chimeric RNA as a diagnostic and prognostic biomarker for prostate cancer in Chinese patients.

Objective To analyze the changes of serum total bilirubin (TBil) and gamma glutamyltransferase (GGT) in patients with type 2 diabetes newly diagnosed without complications and explore their relationship with vascular complications of type 2 diabetes.Methods The levels of serum TBil and GGT were determined by automatic biochemical analyzer in 42 healthy person (control group),64patients with type 2 diabetes without complications (diabetes without complications group) and 81 patients with type 2 diabetes with vascular complications (diabetes with complications group).Results The levels of serum TBil and GGT were (7.89 ± 4.81) μ mol/L and (29.81 ± 14.97) U/L in diabetes with complications group.The level of serum TBil was (10.42 ± 3.55) μ mol/L in control group.The levels of serum TBil and GGT were (11.30 ± 4.16) μ mol/L and (47.00 ± 38.57) U/L in diabetes without complications group.The level of serum TBil in diabetes with complications group was lower than that in control group and diabetes without complications group (P ＜ 0.05).The level of serum GGT in diabetes with complications group was lower than that in diabetes without complications group (P ＜ 0.05).Pearson correlation analysis showed that 24-hour urinary protein excretion,urinary albumin creatinine ratio had negative correlation with serum TBil (P ＜0.05).Logistic regression analysis showed that GGT was the protective factor of diabetic vascular complications (OR =0.965).Conclusion The levels of serum TBil and GGT may be associated with the occurrence and development of vascular lesions in patients with type 2 diabetes. Key words: Diabetes mellitus,type 2; Bilirubin; Gamma-glutamyltransferase; Oxidative stress

Background & Objective: Pregnancy-induced hypertensive disorders (PIHD) are the main reasons for maternal and perinatal mortality, as they complicate 10% of pregnancies worldwide. Serum lactic acid dehydrogenase (LDH) and gamma-glutamyl transferase (GGT) are possible markers reflecting the occurrence of pregnancy-associated complications like preeclampsia and eclampsia. There is a paucity of data with conflicting results showing serum LDH and GGT on PIHD in Ethiopia. This investigation aimed to assess the serum LDH and GGT levels in pregnant women with PIHD along with their correlation with the severity of the disease at Jimma Medical Center (JMC), Ethiopia.Materials & Methods: This hospital-based comparative cross-sectional study was undertaken from August 03 to September 27, 2020, in JMC. A total of 97 study participants were recruited. Serum GGT and LDH levels were determined using a fully automated Roche Cobas 6000 chemistry analyzer. The data were analyzed using SPSS 25.0. One-way ANOVA and independent samples t-test were employed to compare serum GGT and LDH levels with categories of PIHD.Results: The significantly highest mean serum levels of LDH (580.9±193.8 U/L) and GGT (86.1±29.2 U/L) were observed in eclamptic women compared to gestational hypertensive (276.7±60.7 and 38.3±16.9 U/L) and preeclamptic patients (353±132.8 and 48.8±29.9 U/L), respectively. Both serum GGT and LDH levels were found to correlate with the severity of preeclampsia, respectively significantly.Conclusion: Serum LDH and GGT were found to be at the highest levels in eclamptic than preeclamptic and gestational hypertensive women. Blood pressure, gestational age, and severity of hypertensive disorders of pregnancy were predictor variables associated with serum GGT and LDH.

Gamma-glutamyl transferase: risk and prognosis of cancer.

Prostate Specific Antigen and Human Glandular Kallikrein 2 in Early Detection of Prostate Cancer

Impaired fasting glucose (IFG), being a pre-diabetic condition, can increase the risk of overt diabetes; thus early detection and prediction of IFG are important to reduce the incidence of overt diabetes. Some predictive factors, including serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), have been reported in several studies, but none of the studies have investigated the effect of longitudinal changes in individual serum ALT and GGT levels on the risk of IFG. We aimed to investigate the association between changes in the serum ALT and GGT levels and the risk of IFG using a checkup database between 1999 and 2014. A total of 3,598 males and 3,275 females were enrolled in the study. We performed a follow-up test of serum ALT or GGT in each individual, and classified the cases in which the serum ALT or GGT level was increased or decreased during the follow-up test compared to the baseline. According to the multivariate Cox proportional hazards model, the hazard ratio was 1.76 (95% confidence interval, 1.45-2.12; P < 0.001) in male subjects with an increased serum GGT level compared to male subjects with a decrease in the serum GGT level at follow-up compared to the baseline. However, the relationship between the serum ALT level and incidence of new-onset IFG was not statistically significant in both sexes; and in females, the relationship between the serum GGT level and incidence of new-onset IFG was also not statistically significant. We revealed that a longitudinal increase in serum GGT levels was related to an increased risk of IFG in males. Therefore, monitoring the changes in serum GGT levels is important for predicting new-onset IFG, and it can be used as an early indicator of onset of overt diabetes in males.

Association between empirically derived dietary patterns and liver function tests in adults: Shahedieh cohort study.

It remains unclear whether the respective dose-response relationships between serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels and risk of mortality are consistent by age. We used sampled cohort data from the National Health Insurance Corporation to conduct a retrospective cohort study. A total of 313 252 participants who received medical health check-ups from 2002 to 2008 were assessed for risk of death according to serum ALT and GGT levels over an average of 6 years. The hazard ratios (HRs) for mortality were analysed with Cox proportional hazard model. The crude mortality rate increased linearly with increasing serum ALT and GGT levels in adults aged <60 years. However, the all-cause mortality rate showed a J-shaped relationship with increasing serum ALT levels whereas all-cause mortality rate showed a linear relationship with increasing serum GGT levels in adults aged ≥60 years. The HR of death showed U-shaped relationships with increasing serum ALT levels in adults aged ≥60 years. On the contrary, the HR of death from any cause had a linear association with increasing serum GGT levels among all age groups. In this study, U-shaped relationship patterns were demonstrated between serum ALT levels and risk for all-cause mortality in adults aged ≥60 years while serum GGT levels showed a linear relationship with risk for all-cause death. Very low levels of serum ALT in elderly patients suggest that they are at high risk of mortality.

Background: This study aimed to assess the applicability of the soluble urokinase plasminogen activator receptor (suPAR) protein as a diagnostic and/or prognostic biomarker for prostate cancer (PCa) patients. Material and Methods: SuPAR levels were evaluated by ELISA in serum samples from 146 PCa patients, 35 benign prostate hyperplasia (BPH) patients and 18 healthy controls. Results: Antigen levels of suPAR differed between healthy controls and PCa or BPH patients (P&amp;lt;0.001). Additionally, suPAR levels differed between the Gleason sum groups GS = 7 vs. GS&amp;gt;7, with higher levels in the latter group (P = 0.011). For further statistical analysis, patients and proband cohorts were separated according to their serum expression of suPAR in a group with low/intermediate level (≤66% percentile) and a group with high levels (&amp;gt;66% percentile). A significant difference in the disease-specific survival was detected between the low/intermediate and the high suPAR level groups (191.4 vs. 144.5 months; P = 0.039; log rank test). The high level group showed a 3.91-fold increased risk of tumor-related death compared to the low/intermediate suPAR level group but this was not significant (P = 0.055; univariate Cox's regression hazard analysis). Therefore, future studies with larger cohorts of PCa patients as well as prospective surveys are necessary. Conclusion: The differences between the PCa/BPH/healthy control cohorts for suPAR in conjunction with the association of high suPAR antigen levels in the serum with a poor prognosis suggest a diagnostic and prognostic impact of this biomarker for PCa patients. Citation Format: Sven Wach, Omar Al-Janabi, Katrin Weigelt, Kersten Fischer, Thomas Greither, Marios Marcou, Gerit Theil, Elke Nolte, Hans-Juergen Holzhausen, Robert Stoehr, Verena Huppert, Arndt Hartmann, Paolo Fornara, Bernd Wullich, Helge W. Taubert. Serum level of urokinase plasminogen activator receptor is suggested as diagnostic and prognostic biomarker in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4823. doi:10.1158/1538-7445.AM2015-4823

ABSTRACTObjective: To investigate the association between serum gamma-glutamyl transferase (GGT) levels and serum uric acid levels in middle-aged and elderly Chinese females. Methods: A cross-sectional population survey was performed in Luzhou, China (2014). Questionnaires, physical examinations and biochemical tests were conducted. Finally, we included 2486 females who were > 40 years old as participants. Multiple linear regression analysis was used to estimate the association of serum acid levels and other variables. Serum GGT levels were divided into four groups using the 25th, 50th and 75th percentiles as cut-off points. Finally, binary logistic regression analysis was used to investigate the association of different serum GGT quartiles with the risk of hyperuricemia. Results: The prevalence of hyperuricemia was 25.1% in the studied population and gradually increased across the serum GGT quartiles (P < 0.05). Binary logistic regression analysis showed that compared with subjects in the lowest quartile of serum GGT levels, the adjusted odds ratio (ORs) for uric acid in the highest quartile was 2.34 (95% confidence interval (CI), 1.68–3.28, P < 0.001),after corrections for TG, TC, HDL-C, LDL-C, creatinine (CR), GGT, AST, ALT, fasting plasma glucose (FPG), postprandial 2-h plasma glucose, hemoglobin A1c(HbA1c), age, BMI, SBP, DBP, waist-to-hip ratio and neck circumference (NC). Conclusions: The serum GGT level is associated with hyperuricemia in middle-aged and elderly Chinese females.

Prostate cancer (PCa) is the second-leading cause of mortality in men and the most commonly diagnosed non-cutaneous male malignancy. Host genetic factors, and inflammation-induced cytokines, play a key role in prostate oncogenesis. Single Nucleotide Polymorphisms (SNP) in cytokine genes were suggested to increase the susceptibility for PCa development and progression. This study aimed to investigate the association between the SNP (rs16944) in the interleukin-1 β (IL-1β) gene and the serum levels of Prostate Specific Antigen (PSA) Prolactine (PRL), testosterone, and IL-1β in Iraqi PCa patients versus healthy controls. Taqman Real Time-PCR, was performed to investigate the IL-1β (rs16944) polymorphism in 100 Iraqi PCa patients and 50 age-matched healthy controls in a case-control study. Serum levels of PSA, PRL, and testosterone were determined by ELISA and FIA, and associated with the IL-1β serum level as well as with the SNP (rs 16944). The association between the clinico-pathological parameters and the genotype distribution of PCa patients was also studied. There level of IL-1β was significant increased in the serum of PCa patients compared to controls (P = 8.19 10-7). Serum levels for other biomarkers such as PSA, PRL and testosterone were also significantly elevated in patients compared to controls (P < 0.0001). No differences were seen for genotype and allele distribution between PCa patients and controls. Nevertheless, in the group of controls, we found that 36% carried the GG genotype against only 26% in the patients group.This suggests that this could be a protective genotype (OR 0.62, P = 0.254). In addition, we found that the GA genotype is slightly more frequent in patients as compared to controls (OR 1.22, P = 0.605). Interestingly, serum levels of IL-1β, PSA, PRL and testosterone were significantly higher in PCa patients carrying the GA genotype, and the GA and AA genotypes are strongly associated with the aggressive behavior of the disease such as advanced TNM, and high Gleason score. Our data suggest that both serum IL-1β level and IL-1β SNP (rs16944) may be considered as candidate biomarkers for PCa. Moreover, the GA, and AA genotypes carriers along with high sera levels of IL-1β, PSA and PRL, have an increased risk for PCa with aggressive behavior in Iraqi men.