title: Clinical significance of LGR5 and CD44 expression in locally advanced             rectal cancer after preoperative chemoradiotherapy.
abstract: LGR5, known as a target of Wnt signaling, has been reported as an intestinal             stem cell marker. Recent reports showed that LGR5 was associated with carcinogenesis             and tumor invasion in colorectal cancer. CD44 is a ubiquitously expressed cell             adhesion molecule and also a potential cell surface marker on colon cancer stem             cells. Both LGR5 and CD44 have been also reported to be Wnt signal targets. The             aim of this study was to investigate the association of these markers with clinical             outcome in rectal cancer after preoperative chemoradiotherapy (CRT). A total of             52 rectal cancer specimens were obtained from patients who underwent preoperative             CRT. We performed transcriptional and immunohistochemical analyses, and retrospectively             studied the association of LGR5 and CD44 expression levels with clinical outcomes.             For CD44, its expression in cancer stroma was also evaluated. The levels of cancer             LGR5 and CD44 gene expression were significantly and positively correlated. LGR5             gene expression level in cancer and positivity of CD44 gene expression in cancer             stroma were significantly correlated with disease recurrence. Elevated cancer             LGR5 gene expression and positive CD44 gene expression in cancer stroma were significantly             associated with poor recurrence-free and overall survival. Multivariate analysis             indicated that positivity of stromal CD44 gene expression was an independent prognostic             factor for the recurrence and overall survival of patients with rectal cancer             after preoperative CRT. In conclusion, LGR5 and CD44 expression may be coordinately             associated with tumor relapse in locally advanced rectal cancer after preoperative             CRT.
authors.affiliation: Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. saigusa@clin.medic.mie-u.ac.jp
authors.forename: Susumu
authors.initials: S
authors.lastname: Saigusa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Inoue
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Yuji
authors.initials: Y
authors.lastname: Toiyama
authors.forename: Kohei
authors.initials: K
authors.lastname: Matsushita
authors.forename: Mikio
authors.initials: M
authors.lastname: Kawamura
authors.forename: Yoshinaga
authors.initials: Y
authors.lastname: Okugawa
authors.forename: Junichiro
authors.initials: J
authors.lastname: Hiro
authors.forename: Keiichi
authors.initials: K
authors.lastname: Uchida
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Mohri
authors.forename: Masato
authors.initials: M
authors.lastname: Kusunoki
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D012008:Recurrence; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: D018960:Hyaluronan Receptors; C116884:LGR5 protein, human; D043562:Receptors, G-Protein-Coupled