MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease
- 2k Downloads
Colorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters.
Expression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages.
Thirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease.
Association of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.
KeywordsColorectal cancer MicroRNA Expression signature Artificial neural networks
We would like to acknowledge the National Breast Cancer Research Institute (NBCRI) for the continued financial support. The authors gratefully acknowledge Ms. Emer Hennessy and Ms. Catherine Curran for continued technical assistance and curation of the Department of Surgery BioBank.
- 1.Garcia M, Jemal A, Ward EM, Center MM, Hao Y, Siegel RL, Thun MJ (2007) Global cancer facts & figures. American Cancer Society, Atlanta, GAGoogle Scholar
- 5.Mamounas E, Wieand S, Wolmark N et al (1999) Comparative efficacy of adjuvant chemotherapy in patients with Duke’s B versus Duke’s C colon cancer: Results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol 17(5):1349–1355PubMedGoogle Scholar
- 6.International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) Investigators (1999) Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol 17(5):1356–1363Google Scholar
- 27.Sobin LH, Wittekind CH (2002) TNM classification of malignant tumors, 6th edn. John Wiley & Sons, New York, pp 170–173Google Scholar
- 31.Figueredo A, Coombes ME, Mukherjee S (2008) Adjuvant therapy for completely resected stage II colon cancer. Cochrane Database Syst Rev 16(3):CD005390Google Scholar
- 48.Huang Z, Huang D, Ni S, Peng Z, Sheng W, Du X (2009) Plasma microRNAs are promising novel biomarkers for early detection of colorectal cancer. Int J Cancer 127(1):118–126Google Scholar