Concurrent CD44s and STAT3 expression in human clear cell renal cellular carcinoma and its impact on survival

Abstract

Although CD44 was overexpressed and considered as a useful prognostic marker in renal cell carcinoma, the prognostic role of CD44s in clear cell renal cell carcinoma (ccRCC) remains controversial. Moreover, the correlation and prognostic significance of CD44s and its downstream signaling target pSTAT3 are unclear in ccRCC. In this study, 75 pairs of carcinoma and paired adjacent non-tumor renal tissue samples were collected from patients with localized ccRCC who underwent a nephrectomy. The expression levels of CD44s and pSTAT3 were analyzed using immunohistochemistry. Correlations between CD44s/pSTAT3 expression and clinical and pathological characteristics were determined using x(2) test, Kaplan-Meier analysis and Cox's proportional hazards model. We found that CD44s is highly expressed in 46.67% of tumor tissues, and its high expression was significantly associated with high tumor grade (P < 0.001), large tumor size (P = 0.009) and advanced T stage (P = 0.004). A strong correlation exists between high expression of CD44s and pSTAT3 (r = 0.4013, P = 0.0004). The joint over expression of CD44s and pSTAT3 was present in 42.66% of tumor specimens and had an additive negative impact on overall survival. Patients with CD44s(high)pSTAT3(high) expression had significantly poor survival as compared to patients with CD44s(low)pSTAT3(low) tumor expression (P = 0.024), though the concurrent overexpression of CD44s and pSTAT3 was not an independent prognostic factor for overall survival. Our data indicate that expression of both CD44s and pSTAT3 in ccRCC is associated with advanced tumor stage and patient survival. The conclusions from this study may improve the prediction of ccRCC prognosis information when CD44s and pSTAT3 expression are evaluated together with classical clinicopathological parameters.

Keywords: CD44s; ccRCC; pSTAT3; prognosis; survival.

Figure 1

Representative images of CD44s immunohistochemistry staining in clear cell renal cell carcinoma tissues. (A) Negative control, (B) non-neoplastic tissue, (C) no staining, (D) weak staining intensity, (E) intermediate staining intensity and (F) strong staining intensity. Bar, 101.3 μm. Magnification: 400X.

Figure 2

CD44s/pSTAT3 expression associated with patients’ overall survival. A: Kaplan-Meier analysis of overall survival in 43 patients comparing high and low CD44s expression groups. B: Kaplan-Meier analysis of overall survival in 43 patients comparing high and low pSTAT3 expression groups. C: Correlation analysis between CD44s and pSTAT3 expression in ccRCC patients. D: Kaplan-Meier analysis of overall survival for 43 patients based on CD44s and pSTAT3 expression. CD44s^highpSTAT3^high: patients with tumors overexpressing both proteins; CD44s^high or pSTAT3^high: patients with tumors overexpressing only one of the two proteins; CD44s^lowpSTAT3^low: patients with tumors low expressing both proteins.