Predictive microRNAs for lymph node metastasis in endoscopically resectable submucosal colorectal cancer.

Abstract

Accurate prediction of regional lymph node metastasis (LNM) in endoscopically resected T1-stage colorectal cancers (CRCs) can reduce unnecessary surgeries. To identify miRNA markers that can predict LNM in T1-stage CRCs, the study was conducted in two phases; (I) miRNA classifier construction by miRNA-array and quantitative reverse transcription PCR (qRT-PCR) using 36 T1-stage CRC samples; (II) miRNA classifier validation in an independent set of 20 T1-stage CRC samples. The expression of potential downstream target genes of miRNAs was assessed by immunohistochemistry. In the discovery analysis by miRNA microarray, expression of 66 miRNAs were significantly different between LNM-positive and negative CRCs. After qRT-PCR validation, 11 miRNAs were consistently significant in the combined classifier construction set. Among them, miR-342-3p was the most significant one (P=4.3×10-4). Through logistic regression analysis, we developed a three-miRNA classifier (miR-342-3p, miR-361-3p, and miR-3621) for predicting LNM in T1-stage CRCs, yielding the area under the curve of 0.947 (94% sensitivity, 85% specificity and 89% accuracy). The discriminative ability of this system was consistently reliable in the independent validation set (83% sensitivity, 64% specificity and 70% of accuracy). Of the potential downstream targets of the three-miRNAs, expressions of E2F1, RAP2B, and AKT1 were significantly associated with LNM. In conclusion, this classifier can predict LNM more accurately than conventional pathologic criteria and our study results may be helpful to avoid unnecessary bowel surgery after endoscopic resection in early CRC.

• Authors: Chan Kwon Jung, Seung-Hyun Jung, Seon-Hee Yim, Ji-Han Jung, Hyun Joo Choi, Won-Kyung Kang, Sung-Won Park, Seong-Taek Oh, Jun-Gi Kim, Sug Hyung Lee, Yeun-Jun Chung
• Journal: Oncotarget (Oncotarget) Vol. 7 Issue 22 Pg. 32902-15 (May 31 2016) ISSN: 1949-2553 [Electronic] United States
• PMID: 27096956 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• E2F1 Transcription Factor
• E2F1 protein, human
• MicroRNAs
• AKT1 protein, human
• Proto-Oncogene Proteins c-akt
• RAP2B protein, human
• rap GTP-Binding Proteins

Topics

• Biomarkers, Tumor (genetics)
• Chi-Square Distribution
• Colectomy (methods)
• Colonoscopy
• Colorectal Neoplasms (genetics, metabolism, pathology, surgery)
• E2F1 Transcription Factor (genetics, metabolism)
• Endoscopic Mucosal Resection
• Female
• Gene Expression Profiling (methods)
• Gene Expression Regulation, Neoplastic
• Gene Regulatory Networks
• Humans
• Immunohistochemistry
• Logistic Models
• Lymphatic Metastasis
• Male
• MicroRNAs (genetics, metabolism)
• Middle Aged
• Neoplasm Staging
• Oligonucleotide Array Sequence Analysis
• Predictive Value of Tests
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Reproducibility of Results
• Retrospective Studies
• Risk Factors
• rap GTP-Binding Proteins (genetics, metabolism)