Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence

AIM： To evaluate the potential of thioredoxin （TXN） and thioredoxin-interacting protein （TXNIP） expression as biomarkers for predicting gastric cancer recurrence. METHODS： TXN and TXNIP expression levels were acquired from gene expression microarray data for 65 human gastric cancer tissues. We determined whether each gene expression level was associated with cancer recurrence and investigated the relationship between the two genes. For validation, the expression levels of TXN and TXNIP were measured by quantitative real- time reverse transcription polymerase chain reaction in 68 independent stage Ⅲ gastric cancer patients. The correlation between gene expression and cancer prog- nosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the ex- pression patterns of each protein. RESULTS： TXN was a prognosis-related gene （P = 0.009）, whereas TXNIP, a TXN inhibitor, demonstrated a negative correlation with TXN in the gene expres- sion microarray data. In the 68 stage Ⅲ patients, the expression levels of both TXN and TXNIP had a sta- tistically significant effect on recurrence-free survival （RFS, P = 0.008 and P = 0.036, respectively）. The low TXN and high TXNIP expression group exhibited a bet- ter prognosis than the other groups, and the high TXN and low TXNIP expression group exhibited a poorer prognosis （P 〈 0.001 for RFS and P = 0.001 for overall survival）. More than half of the patients in the simulta- neously high TXN and low TXNIP expression group ex- perienced a recurrence within 1 year after curative sur- gery, and the 5-year survival rate of the patients in this group was 29%, compared with 89% in the low TXN and high TXNIP expression group. The TXN protein was overexpressed in 65% of the gastric cancer tis- sues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many on- cogenes and tumor suppressors as well as with genes related to energy, protein synthesis and autophagy. CONCLUSION： TXN and TXNIP are promising prog- nostic markers for gastric cancer, and performing per- sonalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.