Clinical significance of LGR5 and CD44 expression in locally advanced rectal cancer after preoperative chemoradiotherapy

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.