title: Proteomics analysis of differential protein expression identifies heat shock protein 47 as a predictive marker for lymph node metastasis in patients with colorectal cancer.
abstract: The discovery of biomarkers to predict the potential for lymph node (LN) metastasis in patients with colorectal cancer (CRC) is essential for developing improved strategies for treating CRC. In the present study, they used isobaric tags for relative and absolute quantitation to conduct a proteomic analysis designed to identify novel biomarkers for predicting LN metastasis in patients with CRC. They identified 60 differentially expressed proteins specifically associated with LN metastasis in CRC patients and classified the molecular and functional characteristics of these proteins by bioinformatic approaches. A literature search led them to select heat shock protein 47 (HSP47) as the most suitable candidate biomarker for predicting LN metastasis. Validation analysis by immunohistochemistry showed that HSP47 expression in patients with CRC and the number of HSP47-positive spindle cells in the tumor stroma were significantly higher compared with those in adjacent normal colonic mucosa, and the number of the latter cells increased with tumor progression. Further, the number of HSP47-positive spindle cells in stroma was a more informative marker for identifying LN metastasis than HSP47expression. Multivariate analysis identified spindle cells that expressed elevated levels of HSP47 as an independent predictive biomarker for CRC with LN metastasis. Moreover, these cells served as an independent marker of disease-free and overall survival of patients with CRC. Their data indicate that the number of HSP47-positive spindle cells in the stroma of CRC may serve as a novel predictive biomarker of LN metastasis, early recurrence and poor prognosis.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Otake
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujikawa
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiro
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ohi
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Center for Molecular Biology and Genetics, Mie University, Tsu, Mie, Japan.
authors.forename: Yuhko
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Center for Molecular Biology and Genetics, Mie University, Tsu, Mie, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Kobayashi
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.affiliation: Center for Gastrointestinal Research & Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute and Charles A Sammons Cancer Center, Baylor University Medical Center, Dallas, TX.
authors.forename: Ajay
authors.initials: A
authors.lastname: Goel
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D003106:Colon / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D050958:HSP47 Heat-Shock Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics*; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000235:genetics; D016016:Proportional Hazards Models; D040901:Proteomics / Q000379:methods*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D017154:Stromal Cells / Q000737:chemistry
chemical_list: D014408:Biomarkers, Tumor; D050958:HSP47 Heat-Shock Proteins; D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: colorectal cancer; heat shock protein 47; iTRAQ; lymph node metastasis