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.
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Chan Kwon
CK
Jung
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.|Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.|Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Seung-Hyun
SH
Jung
Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Seon-Hee
SH
Yim
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Ji-Han
JH
Jung
Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Hyun Joo
HJ
Choi
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Won-Kyung
WK
Kang
Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.|Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Sung-Won
SW
Park
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Seong-Taek
ST
Oh
Department of Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Jun-Gi
JG
Kim
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.|Cancer Evolution Research Center, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Sug Hyung
SH
Lee
Department of Microbiology, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.|Integrated Research Center for Genome Polymorphism, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Yeun-Jun
YJ
Chung
D014408:Biomarkers, Tumor / Q000235:genetics*; D016009:Chi-Square Distribution; D003082:Colectomy / Q000379:methods; D003113:Colonoscopy; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000069916:Endoscopic Mucosal Resection; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D020668:rap GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D035683:MicroRNAs; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; C065562:RAP2B protein, human; D020668:rap GTP-Binding Proteins
endoscopically resectable colorectal cancer; lymph node metastasis; microRNA