title: Impact of IGF-1, IGF-1R, and IGFBP-3 promoter methylation on the risk and prognosis of esophageal carcinoma.
abstract: The aim of this study is to investigate IGF-1, IGF-1R, and IGFBP-3 methylations in esophageal carcinoma (EC) patients and their relationship with the development and prognosis of EC. This study population consisted of 264 patients (case group) whom EC radical resection was performed and 283 healthy individuals (control group). Methylation-specific PCR (MSP) detected the methylation status of IGF-1, IGF-1R, and IGFBP-3 in the peripheral blood in both groups. The expressions of IGF-1, IGF-1R, and IGFBP-3 in EC and adjacent normal tissues were detected by immunohistochemistry (IHC). The methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 in the case group were higher than those in the control group (all P < 0.05). Additionally, there were statistical significances for the methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 IGF-1 among patients of different clinicopathological features (all P < 0.05). The positive expression rates of IGF-1 and IGF-1R in EC were significantly higher than those in adjacent normal tissues (both P < 0.001), and the rate of IGFBP-3 in EC was significantly lower than that in adjacent normal tissues (P < 0.05). Correlation analysis showed that IGF-1 and IGF1R gene promoter methylation was positively correlated with the positive expressions of IGF-1 (r = 0.139, P = 0.024) and IGF-1R (r = 0.135, P = 0.028), while the IGFBP3 methylation was negatively correlated with the positive expression of IGFBP3 (r = -0.133, P = 0.031). The positive expressions of IGF-1, IGF-1R, and IGFBP-3 were related to different clinicopathological features (all P < 0.05). Cox multivariate analysis results showed that methylation status of IGF-1, IGF-1R, and IGF-1 + IGF1R + IGFBP3 ; expressions of IGF-1 and IGF-1R protein; infiltration depth; and lymph node metastasis (LNM) were independent factors of EC prognosis. Our study demonstrated that methylation of IGF-1, IGF1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 was closely linked with the occurrence of EC and patients' clinicopathological features. Besides, the methylation status of the target genes and the expressions of IGF-1 and IGF-1R protein were independent factors of EC prognosis, which could provide a direction for the prognosis and treatment of EC.
authors.affiliation: Department of Thoracic Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Ye
authors.affiliation: Department of Thoracic Surgery, Cancer Hospital of Harbin Medical University, Haping Road, No. 150, Nangang Area, Harbin, 150080, People's Republic of China. quchangfa1113@163.com.
authors.forename: Chang-Fa
authors.initials: CF
authors.lastname: Qu
authors.affiliation: Department of Thoracic Surgery, The No. 1 People's Hospital of Zhangjiagang, Zhangjiagang, 215600, China.
authors.forename: Xue-Lin
authors.initials: XL
authors.lastname: Hu
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D019175:DNA Methylation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D056726:Genetic Association Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics* / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models; D017526:Receptor, IGF Type 1 / Q000235:genetics* / Q000378:metabolism; D012306:Risk; D012307:Risk Factors
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1
keywords: Clinicopathological features; Esophageal carcinoma; IGF-1; IGF-1R; IGFBP-3; Methylation; Prognosis