Identification of Nkx2–3 and TGFB1I1 expression levels as potential biomarkers to predict the effects of FOLFOX4 chemotherapy

Abstract

This study was designed to detect global gene expressions of primary advanced colorectal cancer (ACC) patients who have undergone FOLFOX4 chemotherapy and screen valuable biomarkers to predict the effects of chemotherapy. Samples from primary ACC patients who have undergone FOLFOX4 chemotherapy were collected. Their chemotherapy effects were evaluated and divided into chemotherapy sensitive group (experimental group) and non-sensitive group (control group). Cancerous tissue gene expression profiles were detected by chip technology. Two groups with differentially expressed genes were screened by cluster analysis and significance analysis of microarrays (SAM). Valuable biomarkers were screened by bioinformatics analysis. Immunohistochemical analysis was performed to characterize the pattern of Nkx2–3 and TGFB1I1 expression. Nkx2–3 and TGFB1I1 signal log ratio were used Receiver Operating Characteristic (ROC) analyses to calculate its own predicting accuracy. Thirty cases were divided into experimental group (13 cases) and control group (17 cases). There was evident difference in the tumor cell biology states of the two groups; that is, 25 ESTs (21 genes) were upregulated and 5 ESTs (5 genes) were downregulated. Nkx2–3 protein was observed on the nucleus of the cancer cells and TGFB1I1 protein was observed on the nucleus and cytoplasm of the cancer cells in experimental group. Their prediction accuracies were 85.3% and 76.7% respectively. Nkx2–3 and TGFB1I1 expressions in control group are very low, but highly expressed in the experimental group; Nkx2–3 and TGFB1I1 may be classified as valuable biomarkers, as these can predict the effects of primary ACC patients who will undergo FOLFOX4.

Keywords: :

• colorectal cancer
• FOLFOX4
• chemotherapy
• gene expression
• biomarker
• Nkx2-3
• TGFB1I1

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

The authors are grateful to the insightful work provided the leaders of Affiliated Union Hospital of Fujian Medical University, all of the fellows in Department of Colorectal and Anal Surgery and students that contributed with some of the studies discussed in this article. The source: National Natural Science Foundation of China. Project Approval number: 30872479; Number of grants: 300,000 RMB. Gainer: Pan Chi.