Predictive Value of Sp1/Sp3/FLIP Signature for Prostate Cancer Recurrence

Abstract

Prediction of prostate cancer prognosis is challenging and predictive biomarkers of recurrence remain elusive. Although prostate specific antigen (PSA) has high sensitivity (90%) at a PSA level of 4.0 ng/mL, its low specificity leads to many false positive results and considerable overtreatment of patients and its performance at lower ranges is poor. Given the histopathological and molecular heterogeneity of prostate cancer, we propose that a panel of markers will be a better tool than a single marker. We tested a panel of markers composed of the anti-apoptotic protein FLIP and its transcriptional regulators Sp1 and Sp3 using prostate tissues from 64 patients with recurrent and non-recurrent cancer who underwent radical prostatectomy as primary treatment for prostate cancer and were followed with PSA measurements for at least 5 years. Immunohistochemical staining for Sp1, Sp3, and FLIP was performed on these tissues and scored based on the proportion and intensity of staining. The predictive value of the FLIP/Sp1/Sp3 signature for clinical outcome (recurrence vs. non-recurrence) was explored with logistic regression, and combinations of FLIP/Sp1/Sp3 and Gleason score were analyzed with a stepwise (backward and forward) logistic model. The discrimination of the markers was identified by sensitivity-specificity analysis and the diagnostic value of FLIP/Sp1/Sp3 was determined using area under the curve (AUC) for receiver operator characteristic curves. The AUCs for FLIP, Sp1, Sp3, and Gleason score for predicting PSA failure and non-failure were 0.71, 0.66, 0.68, and 0.76, respectively. However, this increased to 0.93 when combined. Thus, the “biomarker signature” of FLIP/Sp1/Sp3 combined with Gleason score predicted disease recurrence and stratified patients who are likely to benefit from more aggressive treatment.

Receptor tyrosine kinase recepteur d'origine nantais as predictive marker for aggressive prostate cancer in African Americans

“…Furthermore, levels of c‐FLIP are also elevated in human prostate tumors including castrate resistant tumors making it a clinically relevant target. Our findings that increased expression of AR, RON, and c‐FLIP in tumors is in line with published studies including our own . However, the present study to the best of our knowledge is the first report showing a correlation between RON/AR with ethnicity.…”

“…AR antibody was from Thermo Fisher Scientific (Waltham, MA; list and source of antibodies is provided as Figure S1). The tissues were stained according to previously published protocols and appropriate negative controls were used . Rabbit horseshoe radish peroxidase polymer and DAB chromogen were used as the ancillary system and hematoxylin was used for counterstaining (Biocare Medical, Concord, CA and DAKO North America Inc. Carpinteria, CA).…”

“…Briefly, the proportion of positive tumor cells was scored as follows: 0, no stained cells; 1, ≤1%; 2, 1 to 10%; 3, 10 to 33%; 4, 33 to 66%; 5, 66 to 100% stained cells. The intensity score (IS) represents the average staining intensity of tumor cells: 0, no staining; 1, weak; 2, moderate; 3, strong staining . The total (TS) ranged from 0 to 8 and was obtained from the sum of proportion score and IS which is the biomarker score.…”

Coexpression and expression quantitative trait loci analyses of the angiogenesis gene-gene interaction network in prostate cancer

“…Specificity protein 1 (Sp1) is a transcription factor that affects the expression of genes involved in various cellular processes and oncogenesis. Further, expression of Sp1 is associated with the prognosis of patients (67) and can contribute to predicted PCa recurrence (68). Among two SNPs in the promoter region of EGFR , -216G/T was located in a Sp1 recognition site.…”

Towards the Prediction of Mutations in Genomic Sequences

“…Furthermore, those types of predictions were based on computational approaches not involving NGS, such as microarray analysis, qPCR, and others [6][7] [8] in various types of cancer such as colorectal [9], lung [10], prostate [11], breast cancer [12] and others.…”