title: Overexpression of heparan sulfate 6-O-sulfotransferase-2 in colorectal cancer.
abstract: The heparan sulfate sulfotransferase gene family catalyzes the transfer of sulfate groups to heparan sulfate and regulates various growth factor-receptor signaling pathways. However, the involvement of this gene family in cancer biology has not been elucidated. It was demonstrated that the heparan sulfate D-glucosaminyl 6-O-sulfotransferase-2 (HS6ST2) gene is overexpressed in colorectal cancer (CRC) and its clinical significance in patients with CRC was investigated. The mRNA levels ofHS6ST2in clinical CRC samples and various cancer cell lines were assessed using a microarray analysis and quantitative RT-PCR, respectively. An immunohistochemical (IHC) analysis of the HS6ST2 protein was performed using 102 surgical specimens of CRC. The correlations between the HS6ST2 expression status and clinicopathological characteristics were then evaluated.HS6ST2mRNA was significantly overexpressed by 37-fold in CRC samples compared to paired colonic mucosa. High levels ofHS6ST2mRNA expression were also observed in colorectal, esophageal and lung cancer cell lines. The IHC analysis demonstrated that HS6ST2 was expressed in the cytoplasmic region of CRC cells, but not in normal colonic mucosal cells. Positive staining for HS6ST2 was detected in 40 patients (39.2%). There was no significant association between the clinicopathological characteristics and HS6ST2 expression. However, positive staining for HS6ST2 was associated with a poor survival (P=0.074, log-rank test). In conclusion, HS6ST2 was found to be overexpressed in CRC and its expression tended to be a poor prognostic factor, although the correlation was not significant. These findings indicate thatHS6ST2may be a novel cancer-related marker that may provide insight into the glycobiology of CRC.
authors.affiliation: Department of Surgery, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Hatabe
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.affiliation: Department of Surgery, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kato
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Marco
authors.initials: M
authors.lastname: DE Velasco
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Sumitomo Bakelite Co., Ltd., Nishi-ku, Kobe 651-2241, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Yamanouchi
authors.affiliation: Sumitomo Bakelite Co., Ltd., Nishi-ku, Kobe 651-2241, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Fukushima
authors.affiliation: Department of Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Pathology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ito
authors.affiliation: Department of Surgery, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okuno
authors.affiliation: Department of Genome Biology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
keywords: colorectal cancer; heparan sulfate; heparan sulfate 6-O-sulfotransferase-2