title: Promoter methylation and expression of SOCS-1 affect clinical outcome and epithelial-mesenchymal transition in colorectal cancer.
abstract: BACKGROUND
  Abnormal DNA methylation can cause gene silencing in colorectal cancer (CRC) patients. A gene that is suspected to have a crucial role in various types of cancers is the suppressor of cytokine signaling 1 (SOCS-1). Thus, this study will analyze the ramifications of SOCS-1 promoter methylation in CRC patients. This study will also test the therapeutic effects of hypomethylation as a possible CRC therapy.
  
  
  METHODS
  First, 97CRC patients' tumor and adjacent normal tissues were collected. Next, the methylation status of the SOCS-1 promoter region was assessed by methylation-specific polymerase chain reaction (MS-PCR); SOCS-1 protein and mRNA expression were also measured. A 48-month median follow-up period was used for the survival analysis of research participants. Lastly, to analyze the changes in cell invasion and migration in conjunction with protein and mRNA expression, the demethylating agent 5-azacytidine was applied in vitro to human CRC cells.
  
  
  RESULTS
  The results showed increased SOCS-1 hypermethylation in CRC samples compared to controls. Methylated SOCS-1 was associated with significant suppression of SOCS-1 expression in tumors. Additionally, SOCS-1 hypermethylation was significantly correlated with lymph node metastasis and TNM stage. The study also found a poor overall survival rate to be significantly correlated with reduced expression of SOCS-1. After 5-azacytidine treatment, reduced in vitro DNA methylation and increased SOCS-1 expression were observed, and decreased cell migration and epithelial-mesenchymal transition biomarker expression alteration were further confirmed.
  
  
  CONCLUSIONS
  In colorectal cancer tissues, the rate of methylation in the SOCS-1 promoter region is high. Through promoter hypermethylation, the SOCS-1 gene was severely down-regulated in the CRC tissue samples, thereby revealing a plausible therapeutic target for CRC therapy.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Kang
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China.
authors.forename: Bao-Qin
authors.initials: BQ
authors.lastname: Gao
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China.
authors.forename: Qing-Hui
authors.initials: QH
authors.lastname: Yang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, PR China.
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Zheng
authors.affiliation: Department of Medical Oncology, Jingmen Traditional Chinese Medicine Hospital, No.15, Baimiao Rd, Jingmen, Hubei 448000, PR China. Electronic address: doctor_hao@yeah.net.
authors.forename: Sha
authors.initials: S
authors.lastname: Hao
mesh_terms: D001374:Azacitidine / Q000494:pharmacology / Q000627:therapeutic use; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000235:genetics* / Q000378:metabolism; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D001374:Azacitidine
keywords: Colorectal cancer; Epithelial-mesenchymal transition; Methylation; Migration; Suppressor of cytokine signaling