TRIM59, a novel multiple cancer biomarker for immunohistochemical detection of tumorigenesis

Abstract

Objectives and designWe identified a novel TRIM59 gene, as an early signal transducer in two (SV40Tag and Ras) oncogene pathways in murine prostate cancer (CaP) models. We explore its clinical applications as a multitumour marker detecting early tumorigenesis by immunohistochemistry (IHC).Setting and participants88 CaP patients were from a tissue microarray (TMA) of radical prostatectomy specimen, 42 patients from a 35 multiple tumour TMA, 75 patients with renal cell carcinoma (RCC) and 92 patients from eight different tumour groups (breast, lung, parotid, gastrointestinal, female genital tract, bladder, kidney and prostate cancer).ResultsTRIM59 upregulation specifically in tumour area was determined by IHC in 291 cases of 37 tumour types. To demonstrate that TRIM59 upregulation is ‘tumour-specific’, we characterised a significant correlation of TRIM59 IHC signals with tumorigenesis and progression, while in control and normal area, TRIM59 IHC signal was all negative or significantly low. TRIM59 protein upregulation in prostate and kidney cancers was detectable in both intensity and extent in early tumorigenesis of prostate intraepithelial neoplasia (p<0.05) and grade 1 of RCC (p<0.05), and stopped until high grades cancer. The results of the correlation in these two large cohorts of tumour types confirmed and repeated murine CaP model studies. Enhanced TRIM59 expression was identified in most of the 37 different tumours, while the highest intensities were in lung, breast, liver, skin, tongue and mouth (squamous cell cancer) and endometrial cancers. Multiple tumour upregulation was further confirmed by comparing relative scores of TRIM59 IHC signals in eight tumours with a larger patient population; and by a mouse whole-mount embryo (14.5 days post conception) test on the origin of TRIM59 upregulation in epithelial cells.ConclusionsTRIM59 may be used a novel multiple tumour marker for immunohistochemical detecting early tumorigenesis and could direct a novel strategy for molecular-targeted diagnosis and therapy of cancer.

TRIM59 regulates autophagy through modulating both the transcription and the ubiquitination of BECN1

“…We identified TRIM59 as a potential tumor-promoting gene, but the precise molecular mechanism was obscure. TRIM59 has been reported to have oncogenic activity in mouse models and can be used as a multiple tumor marker for detecting early tumorigenesis [29,30]. In gastric tumors, TRIM59 promotes gastric carcinogenesis through ubiquitinating and degrading TP53 [11].…”

TRIM13 Is a Negative Regulator of MDA5-Mediated Type I Interferon Production

“…Trim59 and Ift80 encode a joint transcript termed Ift80L, the mutation of which may be associated with some cases of Jeune syndrome, a developmental disease in humans (18). TRIM59 has also been implicated in cancer as a target of c-Myc repression and a biomarker of tumorigenesis (19,20).…”

A Comparative study of clinicopathological significance, BIRC7, and STC2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder

“…From these sections we assessed 400 tumor cells by semi-quantitative measurements performed in 10 random high power fields, taking into account the number of positively stained and intensity of staining. Cases with positive cells ≥ 25% were considered positive, while cases with positive cells < 25% were considered negative [33][34]. All relative scores were accessed by two pathologists independently.…”