title: Transcriptome analysis of CD133-positive stem cells and prognostic value of survivin in colorectal cancer.
abstract: OBJECTIVE
  CD133 is an important, but not exclusive, biomarker of colorectal cancer (CRC) stem cells.
  
  
  METHODS
  In order to identify other CRC stem cell-specific genes, we performed a comparative expression profiling of CD133(+) and CD133(-) cell populations in primary and metastatic tumors from four patients with CRC. CD133(+) and CD133(-) CRC cells were isolated using MagSweeper and used for whole-transcriptome analysis with RNA-Seq.
  
  
  RESULTS
  We found that in CD133(+) cells, 17 genes (RNASE2, PRB2, IL4, MGC27382, CLEC4C, SALL3, GIMAP1, ISG15, LOC728875, ZIK1, ICAM2, CCDC7, CDYL2, LRRC2, ZEB1, OSTF1 and CCDC144B) were significantly up-regulated compared to CD133(-) CRC cells. Among them, IL4 has been known as an inducer of survivin implicated in the survival and proliferation of cancer cells. However, the prognostic value of survivin in CRC is controversial. We evaluated survivin expression in formalin-fixed paraffin-embedded tumor samples of 188 patients with CRC by immunohistochemistry. Survivin over-expression was detected in 85 patients (45.2%) and was significantly associated with primary tumor sites (p=0.028), lymph node metastasis (p=0.029) and advanced III/IV CRC stages (AJCC 7; p=0.001). Furthermore, survivin up-regulation correlated with reduced disease-free survival (DFS; p=0.021) and overall survival (OS; p<0.000) and was proved to be an independent prognostic factor for both DFS and OS in multivariate analysis.
  
  
  CONCLUSIONS
  Our data suggest that CD133(+) CRC stem cells have a distinct expression pattern and that survivin, up-regulated by differentially expressed IL-4, is a candidate biomarker for the prediction of recurrence and survival in CRC.
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Seung Tae
authors.initials: ST
authors.lastname: Kim
authors.affiliation: Center for Biostatistics and Clinical Epidemiology, Samsung Medical Cancer, Seoul, Republic of Korea.
authors.forename: Insuk
authors.initials: I
authors.lastname: Sohn
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: In-Gu
authors.initials: IG
authors.lastname: DO
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jiryeon
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Seok Hyung
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Center for Biostatistics and Clinical Epidemiology, Samsung Medical Cancer, Seoul, Republic of Korea Samsung Advanced Institute for Health Science and Technology, Sungkyunkwan University, Seoul, Republic of Korea.
authors.forename: In Ho
authors.initials: IH
authors.lastname: Jung
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.affiliation: Stanford Genome Technology Center, Department of Genetics, Stanford University, Stanford, CA, U.S.A.
authors.forename: Amirali
authors.initials: A
authors.lastname: Talasaz
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Colorectal Surgery, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Colorectal Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Hee Cheol
authors.initials: HC
authors.lastname: Kim
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000502:physiology; D010455:Peptides / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D000077022:Survivin; D059467:Transcriptome
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D006023:Glycoproteins; D051034:Inhibitor of Apoptosis Proteins; C000606023:PROM1 protein, human; D010455:Peptides; D000077022:Survivin
keywords: CD133+; Cancer stem cells; interleukin-4; surviving