title: CDH13 and FLBN3 gene methylation are associated with poor prognosis in colorectal cancer.
abstract: The aim of this study was to identify potential epigenetic prognostic biomarkers for colorectal cancer (CRC) in the Chinese population. The methylation status of five tumor suppressor genes (CDH13, DLEC1, FBLN3, hMHL1 and RUNX3) was determined using manual microdissection followed by methylation-specific PCR in 85 paired CRC specimens and adjacent normal tissue. The results showed that methylation frequencies in cancerous tissues were 31.8% for CDH13, 37.6% for DLEC1, 38.8% for FBLN3, 22.4% for hMHL1 and 27.1% for RUNX3, all of which were significantly higher than in corresponding normal tissue. Furthermore, CDH13 methylation was associated with poor differentiation (P = 0.019) and tended to be predominant in advanced stages (P = 0.084); FBLN3 methylation was associated with advanced stages (P = 0.027) and lymph node metastasis (P = 0.029). Accordingly, the methylation status of CDH13 (P = 0.022), FBLN3 (P = 0.008), CDH13 and/or FBLN3 (P = 0.001) predicted adverse overall survival in CRC, while hMHL1 methylation showed a protective role in survival (P = 0.046). Cox proportional hazard models further indicated that CDH13 and/or FBLN3 methylation, but not that of hMHL1, was an independent prognostic factor for CRC. In conclusion, we found CDH13 and FBLN3 gene methylation are potential biomarkers for poor prognosis in CRC.
authors.affiliation: Department of Oncology, Yangzhou No.1 People's Hospital, The second Clinical School of Yangzhou University, Number 368, Mid Hanjiang Road, Yangzhou, 225009, China. wangzhu@csco.org.cn
authors.forename: Zhu
authors.initials: Z
authors.lastname: Wang
authors.forename: Xin
authors.initials: X
authors.lastname: Yuan
authors.forename: Nanlin
authors.initials: N
authors.lastname: Jiao
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Youwei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jiandong
authors.initials: J
authors.lastname: Tong
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics*; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D057890:Epigenomics; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D012007:Rectum / Q000378:metabolism; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; C099972:H-cadherin; D004247:DNA