J 2021

Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer

WIEBRINGHAUS, R., M. PECORARO, H.A. NEUBAUER, Karolína TRACHTOVÁ, B. TRIMMEL et. al.

Základní údaje

Originální název

Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer

Autoři

WIEBRINGHAUS, R., M. PECORARO, H.A. NEUBAUER, Karolína TRACHTOVÁ (203 Česká republika, garant, domácí), B. TRIMMEL, M. WIESELBERG, J. PENCIK, G. EGGER, C. KRALL, R. MORIGGL, M. MANN, B. HANTUSCH a L. KENNER

Vydání

Cancers, BASEL, MDPI, 2021, 2072-6694

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 6.575

Kód RIV

RIV/00216224:14740/21:00124264

Organizační jednotka

Středoevropský technologický institut

UT WoS

000735678200001

Klíčová slova anglicky

prostate cancer; FFPE-proteomics; OXPHOS; NDUFS1; ATP5O; STAT3; transcriptomics

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 23. 2. 2022 13:41, Mgr. Pavla Foltynová, Ph.D.

Anotace

V originále

Simple Summary Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers-NDUFS1 and ATP5O-for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level. We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients.