“ Evaluating Engrailed-2 and Cytokines in urine with serum PSA as potential biomarkers in patients with prostatism at MTRH Eldoret, Kenya”

Abstract

Background: Majority of adult male patients in the developing world present in clinics with advanced stage prostate cancer (CaP) leading to high mortality and a heavy cancer burden. PSA is currently used for CaP screening and is produced by both malignant and non-malignant cells. PSA levels do not provide information to distinguish among benign prostatic hyperplasia (BPH), prostatitis or malignancy. PSA is therefore prostate-specific,but not prostate cancer–specific. Engrailed-2 (EN-2) is an important protein in the development of the human embryo and a candidate oncogene in prostate cancer; its production is switched off at birth. It is a homeodomain-containing transcription factor,expressed in CaP cell lines. The influx of inflammatory cells, macrophages and lymphocytes, produces pro-inflammatory cytokines like IL-6 and TNF-α that insult normal prostatic tissue propagating the inflammatory process. Objective: To evaluate EN-2 and Cytokines in urine with serum PSA as potential biomarkers in patients with prostatism at Moi Teaching and Referral Hospital Eldoret-Kenya. Methods and procedures: This cross-sectional study involved 39 male adult patients, 13cases-CaP and 26 controls-(24 with BPH & 2 with prostatitis), matched by age. These patients were recruited from the Moi Teaching and Referral Hospital (MTRH) urology clinic and male surgical ward between October and December 2013. A questionnaire was used to record demographic and clinical information about the patients. Digital recta lexamination (DRE) for each patient was conducted by a urologist and results were obtainedfrom the patients chart. Participants were asked to provide an early morning urine specimen in a sterile container. The concentrations of EN-2, IL-6 and TNF-α were determined from the urine deposit using ELISA. Serum PSA results were obtained from the Immunology laboratory. Pelvic/abdominal ultrasound reports were retrieved from the patient‘s file.Results The mean age of cases was 73.1years and controls 71.1 years. Over 92.3% of the cases and73.1% of controls had PSA values >4.0ng/ml. Both cases and controls had elevated levelsof EN-2 in their urine. The difference was not statistically significant. There was no correlation between urinary EN-2 and serum PSA. IL-6 and TNF-α expressions were higher in cases compared to controls (p-values 0.0001 and 0.004 respectively), and these differences were statistically significant. Conclusion and Recommendations: This study shows that EN-2 expression in urine was not a predictive marker as it was elevated in both cases and controls. IL-6 and TNF-α levels were elevated in urine of CaPpatients. The potential for using these cytokines as urinary biomarkers in CaP should be further explored. We recommend a prospective study recruiting a larger number of participants for evaluating EN-2 and cytokines in urine, using histology of prostate biopsy as a gold standard test. Limitations: Most of the patients sought medical attention late and presented at the clinicwhen the disease had already progressed. Biopsies were not available for these patients