title: Integrated Analysis Identifies Molecular Signatures and Specific Prognostic Factors for Different Gastric Cancer Subtypes.
abstract: BACKGROUND
  Gastric cancer (GC) is the fifth leading cause of cancer-related deaths worldwide. As an effective and easily performed method, microscopy-based Lauren classification has been widely accepted by gastrointestinal surgeons and pathologists for GC subtyping, but molecular characteristics of different Lauren subtypes were poorly revealed.
  
  
  METHODS
  GSE62254 was used as a derivation cohort, and GSE15459 was used as a validation cohort. The difference between diffuse and intestinal GC on the gene expression level was measured. Gene ontology (GO) enrichment analysis was performed for both subgroups. Hierarchical clustering and heatmap exhibition were also performed. Kaplan-Meier plot and Cox proportional hazards model were used to evaluate survival grouped by the given genes or hierarchical clusters.
  
  
  RESULTS
  A total of 4598 genes were found differentially expressed between diffuse and intestinal GC. Immunity- and cell adhesion-related GOs were enriched for diffuse GC, whereas DNA repair- and cell cycle-related GOs were enriched for intestinal GC. We proposed a 40-gene signature (χ2=30.71, P<.001) that exhibits better discrimination for prognosis than Lauren classification (χ2=12.11, P=.002). FRZB [RR (95% CI)=1.824 (1.115-2.986), P=.017] and EFEMP1 [RR (95% CI)=1.537 (0.969-2.437), P=.067] were identified as independent prognostic factors only in diffuse GC but not in intestinal GC patients. KRT23 [RR (95% CI)=1.616 (0.938-2.785), P=.083] was identified as an independent prognostic factor only in intestinal GC patients but not in diffuse GC patients. Similar results were achieved in the validation cohort.
  
  
  CONCLUSIONS
  We found that GCs with different Lauren classifications had different molecular characteristics and identified FRZB, EFEMP1, and KRT23 as subtype-specific prognostic factors for GC patients.
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Min
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Biomedical Informatics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Xintao
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xing
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China. Electronic address: slong.guo@163.com.
authors.forename: Shuilong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, PR China. Electronic address: zhangshutian@ccmu.edu.cn.
authors.forename: Shutian
authors.initials: S
authors.lastname: Zhang