Evaluation of tripartite motif 59 and its diagnostic utility in benign bowel diseases and colorectal cancer

J Biochem Mol Toxicol. 2022 Jul;36(7):e23065. doi: 10.1002/jbt.23065. Epub 2022 Apr 4.

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in developing countries. Tripartite motif-59 (TRIM59) a member of the TRIM ubiquitin ligase family, is a surface molecule that regulates biological processes such as cell proliferation, apoptosis, and tumorigenesis. Previous studies reported that TRIM59 expression was upregulated in human CRC, however, the expression pattern and role of TRIM59 in benign colorectal lesions remain unclear. Sixty patients diagnosed with CRC and 60 patients with benign lesions (Crohn's disease, ulcerative colitis, adenoma, and familial adenomatous polyposis) were recruited to the present study. TRIM59 gene expression was assessed by real-time quantitative polymerase chain reaction. Expression of TRIM59 protein and p-AKT were determined using, enzyme-linked immunoassay while p53 expression was detected by immunohistochemistry. Antioxidant/oxidant role of glutathione (GSH)/malondialdehyde (MDA) were evaluated by colorimetric methods in all of the studied groups. Our results showed upregulated expressions of TRIM59 gene and protein levels in CRC tissues and benign colonic lesions compared to nontumor tissues. Their levels were higher in inflammatory compared to noninflammatory bowel lesions. There were significant interrelations among TRIM59 gene expression, protein levels, tumor, node, metastasis staging, and the presence of metastasis (p < 0.0001). Receiver-operator characteristic curve analyses showed that at the cutoff point of 2.5 TRIM59 mRNA expression can discriminate between CRC cases and benign bowel group (area under the curve [AUC]: 0.639, sensitivity: 86.7%, specificity: 41.7%), and between CRC and controls (AUC: 0.962, sensitivity: 90%, specificity: 91.7%). TRIM59 could be a potential biomarker in the early detection, diagnosis, and treatment of benign colonic lesions and CRC.

Keywords: TRIM59; biomarker; colorectal cancer.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Membrane Proteins / genetics
  • Metalloproteins* / genetics
  • Metalloproteins* / metabolism
  • Tripartite Motif Proteins / genetics
  • Tripartite Motif Proteins / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Metalloproteins
  • TRIM59 protein, human
  • Tripartite Motif Proteins