DOI: 10.1101/508754Dec 30, 2018Paper

Prohibitin is a prognostic marker of relapse and therapeutic target to block chemotherapy resistance in Wilms tumor

BioRxiv : the Preprint Server for Biology
Michael V OrtizAlex Kentsis


Wilms tumor (WT) is the most common childhood kidney cancer. To improve risk stratification and identify novel therapeutic targets for patients with WT, we used high-resolution mass spectrometry proteomics to identify urine tumor markers associated with WT relapse. We determined urine proteomes at diagnosis of 49 patients with WT, non-WT renal tumors, and age-matched controls, leading to the quantitation of 6,520 urine proteins. Supervised analysis revealed specific urine markers of renal rhabdoid tumors, kidney clear cell sarcomas, renal cell carcinomas, as well as those detected in cured and relapsed WT. In particular, urine prohibitin was significantly elevated at diagnosis in patients with relapsed as compared to cured WT. In a validation cohort of 139 patients, a specific urine prohibitin enzyme-linked immunosorbent assay demonstrated that prohibitin concentrations greater than 998 ng/mL at diagnosis were significantly associated with ultimate WT relapse. Immunohistochemical analysis revealed that prohibitin was highly expressed in primary WT specimens and associated with disease stage. Using functional genetic experiments, we found that prohibitin was required for the growth and survival of WT cells. Overexpression of pro...Continue Reading

Related Concepts

Biological Markers
Renal Cell Carcinoma
Cytochromes c
Enzyme-Linked Immunosorbent Assay
Kidney Failure, Chronic
Kidney Neoplasm

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