title: Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study.
abstract: Cancer stem cells (CSCs) are thought as the source of tumor maintaining and many CSCs markers have been identified. Regarding the heterogeneity in gastric cancer (GC), TNM stage is not enough to accurately predict the prognosis. The aim of this study was to investigate the clinical significance of CSCs markers (Lgr5, Oct4, CD133, EpCAM, CD54 and Sox2) and establish a new model based on these markers to accurately predict prognosis of GC. We retrospectively enrolled 377 GC tissues from January 2006 to October 2012 to perform immunohistochemistry (IHC), and 93 pairs of GC tissues and corresponding adjacent normal gastric tissues to perform quantitative PCR (qPCR) from December 2011 to October 2012. The clinicopathological and follow-up characteristics were collected. In IHC, Oct4, CD133 and EpCAM were independently related to tumor progression, while Sox2 were associated with well or moderate differentiation (all p<0.05). Cox regression showed that Oct4-EpCAM was an independently prognostic factor, indicating that double low expression of Oct4-EpCAM group had significantly better prognosis than control group (p=0.035). Regarding qPCR, CD133 was an independent prognostic factor, showing that the prognosis of patients with CD133 high expression was significantly worse than that of patients with CD133 low expression (p<0.001). The prognostic prediction accuracy of nomogram based on Oct4-EpCAM expression in IHC was significantly better than TNM stage alone (p=0.003). Low expressions of Oct4-EpCAM in IHC and CD133 in qPCR were favorable prognostic factors in GC. The nomogram based on Oct4-EpCAM was valuable in prognostic prediction of GC patients.
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xin-Zu
authors.initials: XZ
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Yi-Gao
authors.initials: YG
authors.lastname: Wang
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Du
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Zheng-Hao
authors.initials: ZH
authors.lastname: Lu
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Wei-Han
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Xue
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Lin-Yong
authors.initials: LY
authors.lastname: Zhao
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yang
authors.affiliation: Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Institute of Digestive Surgery, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Zong-Guang
authors.initials: ZG
authors.lastname: Zhou
authors.affiliation: Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.|Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Jian-Kun
authors.initials: JK
authors.lastname: Hu
authors.affiliation: Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Mo
mesh_terms: D000071916:AC133 Antigen / Q000235:genetics / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D000071858:Epithelial Cell Adhesion Molecule / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors
keywords: cancer stem cells; gastric cancer; markers; nomogram; prognosis