Brief Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Oct 21, 2012; 18(39): 5581-5588
Published online Oct 21, 2012. doi: 10.3748/wjg.v18.i39.5581
Thioredoxin and thioredoxin-interacting protein as prognostic markers for gastric cancer recurrence
Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho
Jae Yun Lim, Jae Yong Cho, Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea
Sun Och Yoon, Soon Won Hong, Department of Pathology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea
Jong Won Kim, Seung Ho Choi, Department of Surgery, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, Seoul 135-720, South Korea
Author contributions: Lim JY and Cho JY designed the study; Lim JY, Yoon SO, Hong SW, Kim JW and Choi SH contributed to performing experiment and acquisition of data; Lim JY, Yoon SO and Cho JY analyzed and interpreted the data; Lim JY and Cho JY wrote the paper.
Supported by The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, No. 2010-0024248; and A Faculty Research Grant from Yonsei University College of Medicine for 2011, No. 6-2011-0113, 6-2011-0146
Correspondence to: Dr. Jae Yong Cho, Department of Medical Oncology, Gangnam Severance Cancer Hospital, Yonsei University College of Medicine, 712 Eonjuro, Gangnam-gu, Seoul 135-720, South Korea. chojy@yuhs.ac
Telephone: +82-2-20194363 Fax: +82-2-34633882
Received: April 27, 2012
Revised: June 29, 2012
Accepted: July 9, 2012
Published online: October 21, 2012
Abstract

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 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.

CONCLUSION: 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.

Keywords: Gastric cancer; Thioredoxin; Thioredoxin-interacting protein; Biomarker; Prognosis