Clinicopathological significance and prognostic implication of CD44 and its splice variants (v3 and v6) in colorectal cancer

CD44 及其剪接变体(v3 和 v6)在结直肠癌中的临床病理意义和预后意义

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作者:Bing Yan #, Ying Mu #, Meiqi Cui, Long Liu

Background

CD44 is a marker for colorectal cancer (CRC) stem cells (CCSCs), but its prognostic value remains controversial. Furthermore, few studies have investigated the expression profile of CD44 variants in CRC. The proto-oncogene mast/stem cell growth factor receptor Kit (c-Kit) was previously found to play an important role in supporting CRC cells; however, the associations between c-Kit and CD44 (and its splice variants) remain largely unknown.

Conclusions

CD44, CD44v3 and CD44v6 were determined to be heterogeneously expressed in CRC, and may aid in the prognostic prediction of patients with this disease.

Methods

A total of 148 patients with CRC were enrolled in the present study, and the levels of CD44, CD44 splice variant (v)3, CD44v6 and c-Kit were examined by immunohistochemical staining. Associations between these markers and clinicopathological parameters, as well as the extent to which these markers predict progression free-survival (PFS), were analyzed.

Results

A total of 29 (19.6%), 60 (40.5%) and 66 (44.6%) patients were CD44-, CD44v3- and CD44v6-positive, respectively. No clear c-Kit-positivity was detected in any of the patients. Analyses of clinicopathological features indicated that positive expression of CD44v3 was significantly associated with cell differentiation (P=0.03), and N (P=0.04), M (P<0.01) and tumor-node-metastasis (TNM) stages (P<0.01). Univariate analysis demonstrated that T, N, M and TNM stages (all P<0.01), and CD44 (P<0.01), CD44v3 (P=0.03) and CD44v6 (P=0.02) levels were significantly associated with PFS. Furthermore, multivariate analysis indicated that patients without CD44 expression (P<0.01) but with CD44v3 (P=0.04) and CD44v6 (P=0.02) expression exhibited significantly shortened PFS. Conclusions: CD44, CD44v3 and CD44v6 were determined to be heterogeneously expressed in CRC, and may aid in the prognostic prediction of patients with this disease.

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