Prognostic value of Musashi-1 in endometrioid adenocarcinoma

Abstract

Aims: Musashi-1, a RNA-binding protein, is suggested to be a cancer stem cell-related marker; its high level of protein expression is reported to be associated with high histological grade in some tumors. The aim of this study was to investigate the prognostic value of Musashi-1 in patients with endometrioid adenocarcinoma (EAC).

Methods: We examined the Musashi-1 mRNA expression level in 35 fresh EAC tissue samples and 15 normal endometrium samples by real-time RT-PCR, and its protein expression level in 148 paraffin EAC tissue samples and 20 paraffin normal endometrium samples by immunohistochemistry. The correlation between Musashi-1 and overall survival (OS) used Cox proportional hazards regression. The prognostic accuracy of Musashi-1 compared with other clinicopathological risk factors by logistic regression. Furthermore, we examined whether Musashi-1 expression is correlated with another cancer stem cell marker CD133 by real-time RT-PCR.

Results: Musashi-1 mRNA expression of EAC is 2.8-fold higher than that of normal endometrium (P=0.0009). Musashi-1 protein expression level is correlated with tumor stage, grade and vascular invasion. Patients with higher protein expression level of Musashi-1 are associated with poor survival rate than those with negative or low level of expression (HR=2.073, P=0.001). The area under the curve (AUC) for Musashi-1 is 0.8, which is higher than other clinicopathological factors (P=0.000). In addition, Musashi-1 mRNA expression seems to be closely correlated with CD133 expression (r=0.7167, P<0.0001).

Conclusions: Our results suggest high level of Musashi-1 protein expression is associated with poor survival in EAC patients, which may be an independent prognostic factor for EAC.

Keywords: Musashi-1; endometrioid adenocarcinoma; prognosis.

Figure 1

Musashi-1 mRNA expression in 35 fresh EAC tissue samples and 15 fresh normal endometrium tissues using real-time RT-PCR. Musashi-1 mRNA expression of EAC is 2.8-fold higher than that of normal endometrium. The data were analyzed using the ΔΔCt approach and expressed as the Musashi-1/β-actin ratio [2-ΔCt (Musashi-1-β-actin)]. (***, P < 0.0009).

Figure 2

Representative image of Musashi-1 expression in EAC tissues was defined as (A), negative staining; (B), low staining; (C), moderate staining and (D), high staining. Original magnification: ×200.

Figure 3

Comparisons of OS between Musashi-1 (Msi-1) negative and positive group in the EAC patients by Kaplan-Meier method and log-rank test (*, P < 0.01).

Figure 4

Prognostic significance of Musashi-1 (Msi-1) expression was assessed for all 148 samples separated according to FIGO stage, grade, vascular invasion and lymphatic metastasis by Kaplan-Meier method and log-rank test. A, B. Comparisons of OS between Msi-1 negative or low staining group and moderate or high groups in the EAC patients with type I (P < 0.0001) and type II-III (P = 0.1041). C, D. Comparisons of OS between Msi-1 negative or low staining group and moderate or high groups in the EAC patients with grade1 (P = 0.0377) and grade2 or 3 (P = 0.0255). E. Comparisons of OS between Msi-1 negative or low staining group and moderate or high groups in the EAC patients without lymphatic metastasis (P = 0.0011). F. Comparisons of OS between Msi-1 negative or low staining group and moderate or high group in the EAC patients without vascular invasion (P = 0.0259).

Figure 5

ROC curve compares the prognostic accuracy of Musashi-1 with clinicopathological risk factors in 148 patients with endometrioid adenocarcinoma. Comparisons of the prognostic accuracy by Musashi-1, stage (I vs II-III), grade (G1 vs G2-G3), vascular invasion (yes vs no), lymphatic metastasis (yes vs no). P values show the AUC at 5 years for Musashi-1 vs the AUC at 5 years for other features. ROC = receiver operator characteristic.

Figure 6

CD133 mRNA expression in 35 fresh EAC tissue samples and 15 fresh normal endometrium tissues using real-time RT-PCR. CD133 mRNA expression of EAC is 5.2-fold higher than that of normal endometrium. The data were analyzed using the ΔΔCt approach and expressed as the CD133/β-actin ratio [2-ΔCt (CD133-β-actin)]. (***, P < 0.0001).