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Abstract Prostate-specific antigen (PSA) screening for prostate cancer (PCa) is limited by the lack of specificity but is further complicated in the benign prostatic hyperplasia (BPH) population which also exhibit elevated PSA, representing a clear unmet need to distinguish BPH from PCa. Herein, we evaluated the utility of FLNA IP-MRM, age, and prostate volume to stratify men with BPH from those with PCa. Diagnostic performance of the biomarker panel was better than PSA alone in discriminating patients with negative biopsy from those with PCa, as well as those who have had multiple prior biopsies (AUC 0.75 and 0.87 compared to AUC of PSA alone 0.55 and 0.57 for patients who have had single compared to multiple negative biopsies, respectively). Of interest, in patients with PCa, the panel demonstrated improved performance than PSA alone in those with Gleason scores of 5–7 (AUC 0.76 vs. 0.56) and Gleason scores of 8–10 (AUC 0.74 vs. 0.47). With Gleason scores (8–10), the negative predictive value of the panel is 0.97, indicating potential to limit false negatives in aggressive cancers. Together, these data demonstrate the ability of the biomarker panel to perform better than PSA alone in men with BPH, thus preventing unnecessary biopsies.

Abstract Background Alterations in the expression of human kallikrein-related peptidases (KLKs) have been described in patients with Alzheimer’s disease (AD). We elucidated the suitability of KLK6, KLK8 and KLK10 to distinguish AD from NC and explored associations with established AD biomarkers. Methods KLK levels in cerebrospinal fluid (CSF), as determined by ELISA, were compared between 32 AD patients stratified to A/T/(N) system with evidence for amyloid pathology and of 23 normal controls with normal AD biomarkers. Associations between KLK levels and clinical severity, CSF and positron emission tomography (PET) based AD biomarkers were tested for. Results Levels of KLK6 and KLK10 were significantly increased in AD. KLK6 differed significantly between AD A+/T+/N+ and AD A+/T−/N+ or NC with an AUC of 0.922. CSF pTau and tTau levels were significantly associated with KLK6 in AD. Conclusions KLK6 deserves further investigations as a potential biomarker of Tau pathology in AD.

Objectives:. Coronavirus disease 2019 patients admitted to the ICU have high mortality. The host response to coronavirus disease 2019 has only been partially elucidated, and prognostic biomarkers have not been identified. We performed targeted proteomics on critically ill coronavirus disease 2019 patients to better understand their pathophysiologic mediators and to identify potential outcome markers. Design:. Blood was collected at predetermined ICU days for proximity extension assays to determine the plasma concentrations of 1,161 proteins. Setting:. Tertiary care ICU and academic laboratory. Subjects:. All patients admitted to the ICU suspected of being infected with severe acute respiratory syndrome coronavirus 2, using standardized hospital screening methodologies, had blood samples collected until either testing was confirmed negative on ICU day 3 (coronavirus disease 2019 negative) or until ICU day 10 if the patient positive (coronavirus disease 2019 positive). Interventions:. None. Measurements and Main Results:. Age- and sex-matched healthy control subjects and ICU patients who were either coronavirus disease 2019 positive or coronavirus disease 2019 negative were enrolled. Cohorts were well-balanced with the exception that coronavirus disease 2019 positive patients suffered bilateral pneumonia more frequently than coronavirus disease 2019 negative patients. Mortality rate for coronavirus disease 2019 positive ICU patients was 40%. Feature selection identified the top performing proteins for identifying coronavirus disease 2019 positive ICU patients from both healthy control subjects and coronavirus disease 2019 negative ICU patients (classification accuracies 100%). The coronavirus disease 2019 proteome was dominated by interleukins and chemokines, as well as several membrane receptors linked to lymphocyte-associated microparticles and/or cell debris. Mortality was predicted for coronavirus disease 2019 positive patients based on plasma proteome profiling on both ICU day 1 (accuracy 92%) and ICU day 3 (accuracy 83%). Promising prognostic proteins were then narrowed down to six, each of which provided excellent classification performance for mortality when measured on ICU day 1 CMRF-35-like molecule, interleukin receptor-12 subunit B1, cluster of differentiation 83 [CD83], family with sequence similarity 3, insulin-like growth factor 1 receptor and opticin; area-under-the-curve =1.0; p = 0.007). Conclusions:. Targeted proteomics with feature classification easily distinguished both healthy control subjects and coronavirus disease 2019 tested negative ICU patients from coronavirus disease 2019 tested positive ICU patients. Multiple proteins were identified that accurately predicted coronavirus disease 2019 tested positive patient mortality.

PURPOSE: Calculation of PSA is possible in human fluids even if it presents in very low concentrations with the help of hypersensitive immunodiagnostic methods. The periurethral glands represent one of the potential sources of urine prostate specific antigen (uPSA) in both sexes but the purpose of studying PSA levels in children is still unclear in the literature. In this pilot study we studied uPSA in a small cohort of normal, pre and post pubertal children, in relation to standard anthropometric variables. MATERIALS AND METHODS: The study cohort consisted of 58 children 5-14 years old (42 boys/16 girls). Height, weight, body mass index (BMI) and the respective stature-for-age, weight-for-age and BMI-for-age percentiles of the sample were determined. uPSA levels were measured using a third generation immunodiagnostic method (DPC Immulite®) that has a lower limit of detection of 3 ng/L. When levels of PSA were above the upper limit of detection, uPSA levels were assessed using the ROCHE technique. RESULTS: uPSA levels tend to be higher in male than female children (p = 0.091, linear regression analysis). uPSA was measurable only in 3/16 girls (18.75%). Measurable uPSA was found in 18/42 boys (42.8%). The range of urine PSA in boys was 0-161000 ng/L (mean 10561.9 ± 31830.48 ng/L). Statistical analysis with linear regression showed correlation with height and age in boys. CONCLUSIONS: The use of hypersensitive assays allows calculation of uPSA in childhood. The values of this variable are measurable in both sexes and related with gender. In boys, uPSA was correlated with age and height but not with other variables tested. Further studies are required to clarify this field.

Background: Azoospermia could be due to either obstruction (obstructive azoospermia: OA) or spermatogenic failure (non-obstructive azoospermia: NOA). Close to 50% of men with NOA have small pockets of sperm in the testis which could be retrieved surgically and then injected into oocytes in a program of intra-cytoplasmic sperm insertion. Presently, there are no accepted non-invasive tests allowing clinicians to predict the success rates of sperm retrieval. Previously, we have identified a germ cell-specific protein TEX101 in semen found in the primary spermatocytes and more mature sperm forms, but not in spermatogonia, Sertoli or Leydig cells. We hypothesized that the semen concentration of TEX101 could be used to predict sperm production in men with NOA. Methods: This was a prospective cohort study on men with NOA being treated at a male infertility centre. Men with NOA planning sperm retrieval provided 1–3 semen samples prior to surgery. Semen TEX101 concentrations were measured by an in-house-developed ELISA assay and compared with the results of the surgery to retrieve sperm. Results: 20/60 karyotypically normal men with NOA had semen TEX101 < LOD ( LOD, sperm was found in 50% (34-66%: 95% CI, sig diff. Fisher’s exact test, p Conclusions: Undetectable (

We report the usefulness of a 3.4-kb mitochondrial genome deletion (3.4mtδ) for molecular definition of benign, malignant, and proximal to malignant (PTM) prostate needle biopsy specimens. The 3.4mtδ was identified through long-extension polymerase chain reaction (PCR) analysis of frozen prostate cancer samples. A quantitative PCR assay was developed to measure the levels of the 3.4mtδ in clinical samples. For normalization, amplifications of a nuclear target and total mitochondrial DNA were included. Cycle threshold data from these targets were used to calculate a score for each biopsy sample. In a pilot study of 38 benign, 29 malignant, and 41 PTM biopsy specimens, the difference between benign and malignant core biopsy specimens was well differentiated (P & .0001), with PTM indistinguishable from malignant samples (P = .833). Results of a larger study were identical. In comparison with histopathologic examination for benign and malignant samples, the sensitivity and specificity were 80% and 71%, respectively, and the area under a receiver operating characteristic (ROC) curve was 0.83 for the deletion. In a blinded external validation study, the sensitivity and specificity were 83% and 79%, and the area under the ROC curve was 0.87. The 3.4mtδ may be useful in defining malignant, benign, and PTM prostate tissues. [ABSTRACT FROM AUTHOR]

Abstract??The regulation of gene expression by steroid hormones plays an important role in the normal development and function of many organs, as well in the pathogenesis of endocrine-related cancers. Previous experiments have shown that many kallikrein genes are under steroid hormone regulation in breast cancer cell lines. We here examine the coordinated expression of multiple kallikrein genes in several breast cancer cell lines after steroid hormone stimulation. Breast cancer cell lines were treated with various steroid hormones and kallikrein (KLK/hK) expression of hK3 (prostate-specific antigen, PSA), hK5, hK6, hK7, hK8, hK10, hK11, hK13, and hK14 was analyzed at the RNA level via RT-PCR and at the protein level by immunofluorometric ELISA assays. We identified several distinct hK hormone-dependent and hormone-independent expression patterns. Hormone-specific modulation of expression was seen for several kallikreins in BT-474, MCF-7, and T-47D cell lines. hK6 was specifically up-regulated upon estradiol treatment in all three cell lines whereas PSA expression was induced by dihydrotestosterone (DHT) and norgestrel stimulation in BT-474 and T-47D. hK10, hK11, hK13, and hK14 were specifically up-regulated by DHT in T-47D and by estradiol in BT-474 cells. Bioinformatic analysis of upstream proximal promoter sequences for these hKs did not identify any recognizable hormone-response elements (HREs), suggesting that the coordinated activation of these four hKs represents a unique expression ?cassette?, utilizing a common hormone-dependent mechanism. We conclude that groups of human hKs are coordinately expressed in a steroid hormone-dependent manner. Our data supports clinical observations linking expression of multiple hKs with breast cancer prognosis. [ABSTRACT FROM AUTHOR]