title: Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence.
abstract: OBJECTIVE
  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 prognosis was evaluated. Immunohistochemical staining was performed to investigate the protein expression levels of TXN and TXNIP and to characterize the expression 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 expression microarray data. In the 68 stage III patients, the expression levels of both TXN and TXNIP had a statistically 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 better 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 simultaneously high TXN and low TXNIP expression group experienced a recurrence within 1 year after curative surgery, 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 tissues, whereas the TXNIP protein was underexpressed in 85% of the cancer cells. In a correlation analysis, TXN and TXNIP were highly correlated with many oncogenes and tumor suppressors as well as with genes related to energy, protein synthesis and autophagy.
  
  
  CONCLUSIONS
  TXN and TXNIP are promising prognostic markers for gastric cancer, and performing personalized adjuvant treatment based on TXN and TXNIP expression levels would be an effective practice in the treatment of gastric cancer.
authors.affiliation: Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jae Yun
authors.initials: JY
authors.lastname: Lim
authors.forename: Sun Och
authors.initials: SO
authors.lastname: Yoon
authors.forename: Soon Won
authors.initials: SW
authors.lastname: Hong
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kim
authors.forename: Seung Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Jae Yong
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011182:Postoperative Care; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D013879:Thioredoxins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; C486715:TXNIP protein, human; D013879:Thioredoxins
keywords: Biomarker; Gastric cancer; Prognosis; Thioredoxin; Thioredoxin-interacting protein