title: Identification of stem-like cells and clinical significance of candidate stem cell markers in gastric cancer.
abstract: The existence of gastric cancer stem cells (CSCs) has not been definitively proven and specific cell surface markers for identifying gastric CSCs have largely not been identified. Our research aimed to isolate potential gastric CSCs and clarify their clinical significance, while defining markers for GCSC identification and verification. Here, we report that spheroid cells possess stem cell-like properties, and overexpress certain stem cell markers. CD133 or CD44-positive cells also exhibit properties of CSCs. The expression of Oct4, Sox2, Gli1, CD44, CD133, p-AKT, and p-ERK was significantly higher in metastatic lesions compared to that in primary lesions. Elevated expression of some of these proteins was correlated with a more aggressive phenotype and poorer prognosis, including Oct4, Sox2, Gli1, CD44, and p-ERK. Multivariate Cox proportional hazards model analysis showed that only CD44 is an independent factor. Knockdown of CD44 down-regulated the stem cell-like properties, which was accompanied by the down-regulation of p-ERK and Oct4. Oct4 overexpression could reverse the decreased CSCs properties induced by CD44 knockdown. Taken together, our research revealed that spheroid cell culture, and CD133 or CD44-labeled FACS methods can be used to isolate gastric CSCs. Some CSC markers have clinical significance in predicting the prognosis. CD44 is an independent prognostic factor and maintains the properties of CSCs in CD44-p-ERK-Oct4 positive feedback loop.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Ruixi
authors.initials: R
authors.lastname: Hua
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Mingzhu
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Jiejun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Cancer Chemotherapy Center, Zhoushan Hospital, Zhejiang, China.
authors.forename: Hongqiang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Yufan
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Cancer Hospital of Fudan University, Shanghai, China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Guo
mesh_terms: D000071916:AC133 Antigen / Q000096:biosynthesis*; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000473:pathology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D018874:Spheroids, Cellular / Q000473:pathology*; D013274:Stomach Neoplasms / Q000401:mortality / Q000473:pathology*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000071676:Zinc Finger Protein GLI1 / Q000096:biosynthesis
chemical_list: D000071916:AC133 Antigen; D014408:Biomarkers, Tumor; C497483:CD44 protein, human; C400551:GLI1 protein, human; D018960:Hyaluronan Receptors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C000606023:PROM1 protein, human; D034741:RNA, Small Interfering; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D000071676:Zinc Finger Protein GLI1; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CD133; CD44; cancer stem cell; gastric cancer; stem cell marker