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

Abstract

Introduction

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.

Materials and methods

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.

Results

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.

Conclusions

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.

Keywords:

• Colorectal cancer
• metastasis
• Nrf2/Keap1 pathway
• TXN/GSH system
• S-glutathionylated protein

Acknowledgements

We thank the Biobank of Chang Gung Memorial Hospital at Keelung for providing the tissues and de-identified clinicopathologic features of CRC subjects.

Author contributions

Conception formation: Chang LC, Fan CW and Tseng WK; Interpretation or analysis of data: Hua CC; Preparation of the manuscript: Chang LC; Revision for important intellectual content: Hua CC; Supervision: Hua CC

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

Due to the regulation of IRB in Chang Gung Memorial Hospital, Keelung, no supporting data it available for public sharing.

Additional information

Funding

This investigation was supported by the Chang Gung Memorial Hospital, Keelung under Grant CMRPG2I0011.