title: FAM46C Serves as a Predictor of Hepatic Recurrence in Patients with Resectable Gastric Cancer.
abstract: BACKGROUND
  Gastric cancer (GC) relapse can occur even if curative resection is achieved. Biomarkers predicting recurrence are needed to provide appropriate postoperative surveillance and perioperative therapeutic strategy.
  
  
  METHODS
  A global expression profiling was performed using tissues from GC patients with synchronous liver-confined metastasis. Family with sequence similarity 46, member C (FAM46C), was identified as a candidate biomarker. mRNA expression analysis, direct nucleotide sequencing, bisulfite sequencing and copy number assays for FAM46C were performed with eleven GC cell lines. Expression levels of FAM46C in primary GC tissues from 129 patients who underwent curative GC resection were determined and correlated with clinicopathological factors, including postoperative outcome.
  
  
  RESULTS
  Levels of FAM46C mRNA differed among GC cell lines. Point mutations in FAM46C were detected in five GC cell lines accompanied with reduced FAM46C transcription. No hypermethylation was found in the promoter region of FAM46C. Copy number alterations were found in six GC cell lines with differing FAM46C transcription levels. Reduced FAM46C mRNA expression levels were detected in 117 (91 %) GC specimens compared with adjacent noncancerous tissues. Low FAM46C expression levels were significantly associated with larger macroscopic GC tumor sizes. The low FAM46C expression group was likely to have shorter disease-free survival than the high group and low FAM46C level was identified as an independent risk factor for recurrence after curative resection. FAM46C expression levels were low in all cases that were later found to have hepatic recurrence.
  
  
  CONCLUSIONS
  Reduced GC expression of FAM46C is a potential biomarker to predict hepatic recurrence after curative gastrectomy.
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Haruyoshi
authors: H
authors: Tanaka
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan. m-kanda@med.nagoya-u.ac.jp.
authors: Mitsuro
authors: M
authors: Kanda
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Dai
authors: D
authors: Shimizu
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Chie
authors: C
authors: Tanaka
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Daisuke
authors: D
authors: Kobayashi
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Masamichi
authors: M
authors: Hayashi
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Naoki
authors: N
authors: Iwata
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Suguru
authors: S
authors: Yamada
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Tsutomu
authors: T
authors: Fujii
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Goro
authors: G
authors: Nakayama
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Hiroyuki
authors: H
authors: Sugimoto
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Michitaka
authors: M
authors: Fujiwara
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yukiko
authors: Y
authors: Niwa
authors: Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Yasuhiro
authors: Y
authors: Kodera
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D009713:Nucleotidyltransferases; D017354:Point Mutation; D011379:Prognosis; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D011506:Proteins; D009713:Nucleotidyltransferases; C000621065:TENT5C protein, human
keywords: Copy Number Alteration; Gastric Cancer; Gastric Cancer Cell Line; Gastric Cancer Patient; Gastric Cancer Tissue