New study below.
I almost skipped the paper - what the heck is Tristetraprolin?
But then I read the first sentence:
"Inflammation is linked to prostate cancer (PrCa) progression and is mediated by Nuclear Factor Kappa B (NFκB)."
Nothing new there, but it's nice to see this in a joint Cleveland Clinic - Johns Hopkins - Dana-Farber - etc. - etc. paper.
"Tristetraprolin is a key node of NFκB activation and we investigated its biological and prognostic role in lethal PrCa."
"In vitro assays assessed the function of tristetraprolin and the association between low mRNA tristetraprolin levels and lethal PrCa (metastatic disease or death) was assessed across independent prostatectomy cohorts: (i) nested case-control studies from Health Professionals Follow-up Study and Physicians' Health Study, and (ii) prostatectomy samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and MSKCC. Tristetraprolin expression levels in prostatectomy samples from patients with localized disease and biopsies of metastatic castration resistant PrCa (mCRPC) were assessed in a Cornell University cohort."
"In vitro tristetraprolin expression was inversely associated with NFκB-controlled genes, proliferation and enzalutamide sensitivity. Men with localized PrCa and lower quartile of tumor tristetraprolin expression had a significant, nearly 2-fold higher risk of lethal PrCa after adjusting for known clinical and histological prognostic features (age, RP Gleason score, T-stage). Tristetraprolin expression was also significantly lower in mCRPC compared with localized PrCa."
"There is a clear need for improved biomarkers to identify patients with localized prostate cancer in need of treatment intensification, such as adjuvant testosterone suppression, or treatment de-intensification, such as active surveillance."
There is also a need for a NF-kB inhibitor to be prescribed to all men after diagnosis IMO. Meanwhile, we have an array of polyphenols that are known to inhibit NF-kB in the lab.
-Patrick
ncbi.nlm.nih.gov/pubmed/304...
Cancer Epidemiol Biomarkers Prev. 2018 Nov 12. pii: cebp.0667.2018. doi: 10.1158/1055-9965.EPI-18-0667. [Epub ahead of print]
Low Tristetraprolin Expression is Associated with Lethal Prostate Cancer.
Gerke T1, Beltran H2, Wang X3, Lee GM4, Sboner A5, Karnes RJ6, Klein EA7, Davicioni E8, Yousefi K9, Ross AE10, Börnigen D11, Huttenhower C11, Mucci LA12, Trock BJ13, Sweeney CJ14.
Author information
1
Cancer Epidemiology, Moffitt Cancer Center.
2
Department of Medicine, Division of Hematology and Medical Oncology, Weill Cornell Medical College.
3
MolecularMD.
4
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School.
5
Pathology and Laboratory Medicine, Weill Cornell Medical College.
6
Urology, Mayo Clinic.
7
Glickman Urological and Kidney Institute, Cleveland Clinic.
8
Clinical Laboratory, GenomeDx Biosciences Inc.
9
Clinical Laboratory, GenomeDx Biosciences Inc kyousefi88@gmail.com.
10
Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University.
11
Biostatistics, HSPH.
12
Department of Epidemiology, Harvard TH Chan School of Public Health.
13
The James Buchanan Brady Urological Institute and Department of Urology, Johns Hopkins University School of Medicine.
14
Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute.
Abstract
PURPOSE:
Inflammation is linked to prostate cancer (PrCa) progression and is mediated by Nuclear Factor Kappa B (NFκB). Tristetraprolin is a key node of NFκB activation and we investigated its biological and prognostic role in lethal PrCa.
METHODS:
In vitro assays assessed the function of tristetraprolin and the association between low mRNA tristetraprolin levels and lethal PrCa (metastatic disease or death) was assessed across independent prostatectomy cohorts: (i) nested case-control studies from Health Professionals Follow-up Study and Physicians' Health Study, and (ii) prostatectomy samples from Cleveland Clinic, Mayo Clinic, Johns Hopkins and MSKCC. Tristetraprolin expression levels in prostatectomy samples from patients with localized disease and biopsies of metastatic castration resistant PrCa (mCRPC) were assessed in a Cornell University cohort.
RESULTS:
In vitro tristetraprolin expression was inversely associated with NFκB-controlled genes, proliferation and enzalutamide sensitivity. Men with localized PrCa and lower quartile of tumor tristetraprolin expression had a significant, nearly 2-fold higher risk of lethal PrCa after adjusting for known clinical and histological prognostic features (age, RP Gleason score, T-stage). Tristetraprolin expression was also significantly lower in mCRPC compared with localized PrCa.
CONCLUSIONS:
Lower levels of tristetraprolin in human PrCa prostatectomy tissue are associated with more aggressive PrCa and may serve as an actionable prognostic and predictive biomarker.
IMPACT:
There is a clear need for improved biomarkers to identify patients with localized prostate cancer in need of treatment intensification, such as adjuvant testosterone suppression, or treatment de-intensification, such as active surveillance. Tristetraprolin levels may serve as informative biomarkers in localized PrCa.
Copyright ©2018, American Association for Cancer Research.
PMID: 30420441 DOI: 10.1158/1055-9965.EPI-18-0667
