Predictive microRNAs for lymph node metastasis in endoscopically resectable submucosal colorectal cancer.
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.
['Jung|Chan Kwon|CK|', 'Jung|Seung-Hyun|SH|', 'Yim|Seon-Hee|SH|', 'Jung|Ji-Han|JH|', 'Choi|Hyun Joo|HJ|', 'Kang|Won-Kyung|WK|', 'Park|Sung-Won|SW|', 'Oh|Seong-Taek|ST|', 'Kim|Jun-Gi|JG|', 'Lee|Sug Hyung|SH|', 'Chung|Yeun-Jun|YJ|']
D014408:Biomarkers, Tumor D016009:Chi-Square Distribution D003082:Colectomy D003113:Colonoscopy D015179:Colorectal Neoplasms D050687:E2F1 Transcription Factor D000069916:Endoscopic Mucosal Resection D005260:Female D020869:Gene Expression Profiling D015972:Gene Expression Regulation, Neoplastic D053263:Gene Regulatory Networks D006801:Humans D007150:Immunohistochemistry D016015:Logistic Models D008207:Lymphatic Metastasis D008297:Male D035683:MicroRNAs D008875:Middle Aged D009367:Neoplasm Staging D020411:Oligonucleotide Array Sequence Analysis D011237:Predictive Value of Tests D051057:Proto-Oncogene Proteins c-akt D015203:Reproducibility of Results D012189:Retrospective Studies D012307:Risk Factors D020668:rap GTP-Binding Proteins
microRNA lymph node metastasis endoscopically resectable colorectal cancer