The level of S-glutathionylated protein is a predictor for metastasis in colorectal cancer and correlated with those of Nrf2/Keap1 pathway

• Published in: Biomarkers Vol. 26; no. 8; pp. 780 - 787
• Main Authors: Chang, Liang-Che, Fan, Chung-Wei, Tseng, Wen-Ko, Hua, Chung-Ching
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17.11.2021
• Subjects: Aged; Blotting, Western; Colorectal cancer; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Glutathione - metabolism; Humans; Kelch-Like ECH-Associated Protein 1 - metabolism; Lymphatic Metastasis; Male; metastasis; Middle Aged; Neoplasm Metastasis; NF-E2-Related Factor 2 - metabolism; Nrf2/Keap1 pathway; Prognosis; Protein Processing, Post-Translational; Proteins - metabolism; S-glutathionylated protein; Signal Transduction; Thioredoxins - metabolism; TXN/GSH system; TXN/GSH system; metastasis; Nrf2/Keap1 pathway; Colorectal cancer; S-glutathionylated protein
• ISSN: 1354-750X; 1366-5804
• DOI: 10.1080/1354750X.2021.1999503

The Nrf2 (nuclear factor erythroid 2-like 2; NFE2L2)/Keap1 (Kelch-like ECH-associated protein 1) pathway and the TXN (thioredoxin)/GSH (glutathione) system interact mutually and regulate cellular redox with impacts on cancer metastasis and S-glutathionylation of protein, which is an indicator of cell distress. This study investigates the levels of proteins in the Nrf2/Keap1 pathway and the TXN/GSH system and SGP (S-glutathionylated protein) in CRC (colorectal cancer) with or without metastasis. The protein levels of Nrf2, Keap1, Bach1 (BTB domain and CNC homolog 1), TXN, TXNRD1 (thioredoxin reductase 1), GSR (glutathione reductase) and SGP with molecular weight 31-172 kDa in the normal and tumour tissues of 64 CRC subjects were determined by Western blot. The protein levels and their T/N (tumour/normal tissue) ratios of the Nrf2/Keap1 pathway, the TXN/GSH system and SGP were correlated to different extents in the tissues of CRC subjects with or without lymph node/distant metastasis. The T/N ratios of SGP (odd ratio: 0.19; 95% CI: 0.04-0.74) and lympho-vascular invasion (4.2; 1.39-13.73) were significant predictors for metastasis. SGPs have protein levels correlated with those of the Nrf2/Keap1 pathway and their T/N ratios are a negative predictor for metastasis in CRC.