title: Prognostic significance of CD44 variant 2 upregulation in colorectal cancer.
abstract: BACKGROUND
  CD133 and CD44 are putative cancer stem cell (CSC) markers in colorectal cancer (CRC). However, their clinical significance is currently unclear. Here, we evaluated primary CRC cell isolates to determine the significance of several CSC markers, including CD133 and CD44, as predictors of tumourigenesis and prognosis.
  
  
  METHODS
  CD133- and CD44-positive cells from fresh clinical samples of 77 CRCs were selected by flow cytometric sorting and evaluated for tumourigenicity following subcutaneous transplantation into NOD/SCID mice. Cancer stem cell marker expression was examined in both xenografts and a complementary DNA library compiled from 167 CRC patient samples.
  
  
  RESULTS
  CD44(+), CD133(+) and CD133(+)CD44(+) sub-populations were significantly more tumourigenic than the total cell population. The clinical samples expressed several transcript variants of CD44. Variant 2 was specifically overexpressed in both primary tumours and xenografts in comparison with the normal mucosa. A prognostic assay using qRT-PCR showed that the CD44v2(high) group (n=84, 5-year survival rate (5-OS): 0.74) had a significantly worse prognosis (P=0.041) than the CD44v2(low) group (n=83, 5-OS: 0.88).
  
  
  CONCLUSIONS
  CD44 is an important CSC marker in CRC patients. Furthermore, CRC patients with high expression of CD44v2 have a poorer prognosis than patients with other CD44 variants.
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ozawa
authors.affiliation: Department of Clinical Oncology, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Regenerative Medicine, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: Y-W
authors.initials: YW
authors.lastname: Zheng
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune Minami-ku Yokohama-shi, Kanagawa-ken 232-0024, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Oshima
authors.affiliation: Department of Regenerative Medicine, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miyata
authors.affiliation: Department of Regenerative Medicine, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nakazawa
authors.affiliation: Department of Regenerative Medicine, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: H-B
authors.initials: HB
authors.lastname: Guan
authors.affiliation: Department of Surgery, Kanagawa Cancer Center, 2-3-2 Nakao Asahi-ku Yokohama-shi, Kanagawa-ken 241-8515, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shiozawa
authors.affiliation: Department of Surgery, Kanagawa Cancer Center, 2-3-2 Nakao Asahi-ku Yokohama-shi, Kanagawa-ken 241-8515, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Akaike
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune Minami-ku Yokohama-shi, Kanagawa-ken 232-0024, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune Minami-ku Yokohama-shi, Kanagawa-ken 232-0024, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ota
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune Minami-ku Yokohama-shi, Kanagawa-ken 232-0024, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune Minami-ku Yokohama-shi, Kanagawa-ken 232-0024, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Kunisaki
authors.affiliation: Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafune Minami-ku Yokohama-shi, Kanagawa-ken 232-0024, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishikawa
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Gastroenterological Surgery, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Endo
authors.affiliation: Department of Regenerative Medicine, Yokohama City University, 3-9 Fukuura Kanazawa-ku Yokohama-shi, Kanagawa-ken 236-0004, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Taniguchi
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000473:pathology; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; C497483:CD44 protein, human; D006023:Glycoproteins; D018960:Hyaluronan Receptors; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse