Angiotensin II type I receptor autoantibodies and prostate cancer: cross-sectional and longitudinal studies.

Published: 17-12-2019| Version 2 | DOI: 10.17632/sjdxg5cc5h.2
Neal Fedarko


Autoantibodies against the angiotensin II type I receptor (AT1R) have been associated with multiple diseases (pre-eclampsia, malignant hypertension, transplant rejection, Huntington’s and Alzheimer’s disease, ovarian cancer) suggesting that while the autoantibodies are not necessarily causative they may promote disease progression. These autoantibodies (AT1RaAbs) bind and chronically activate the receptor increasing inflammatory burden. The prostate has a local renin angiotensin system that has been implicated in prostate cancer growth. Two distinct datasets were used to examine the associations between AT1RaAbs and prostate cancer. A cross-sectional set (n = 151) consisting of 101 serum specimens that were collected from patients with scheduled appointments for either elevated prostate specific antigen levels, a scheduled prostate biopsy or being seen as a newly diagnosed PCA patient in a Urology Outpatient Clinic. 80 of these patients were positive for PCA at biopsy, whereas 21 were biopsy benign (either atrophy, benign prostatic hyperplasia, high-grade prostatic intraepithelial neoplasia or inflammation). The remaining 50 specimens were collected from men visiting an offsite prostate cancer screening who were free of prostate disease. Comparisons of covariate values between groups were by Kruskal-Wallis ANOVA with Dunn’s multiple comparisons test. Pairwise correlations between AT1RaAb and clinical correlates or pathological measurements were assessed using Spearman rank correlations. The longitudinal set of pre-diagnosis serum samples from 109 men was obtained from the Baltimore Longitudinal Study of Aging. This prospective cohort study is run by the National Institute on Aging, National Institutes of Health. Clinical measures associated with each BLSA serum sample include age, BMI, blood pressure, PSA levels and, for subjects who later developed PCA, the diagnosis date. All serum is from subjects now deceased with known date of death and post-mortem pathological status of the prostate (disease-free or PCA present). Time to events (diagnosis or death) were modeled nonparametrically by Kaplan-Meier survival curves, dichotomizing samples into either low or high AT1RaAb levels and analyzing serum samples grouped as most proximal or distal to timed event. Accelerated failure estimates were used to assess the effects of other predictors on AT1RaAb association with disease-free and overall survival at most proximal or most distal time points. The datasets correspond to the a study described in the Journal of Translational Autoimmunity published online 13 August 2019, 10000. "Angiotensin receptor autoantibodies as exposures that modify disease progression: cross sectional, longitudinal and in vitro studies of prostate cancer."