CMG2 Expression Is an Independent Prognostic Factor for Soft Tissue Sarcoma Patients

Abstract

The capillary morphogenesis gene 2 (CMG2), also known as the anthrax toxin receptor 2 (ANTXR2), is a transmembrane protein putatively involved in extracellular matrix (ECM) adhesion and tissue remodeling. CMG2 promotes endothelial cell proliferation and exhibits angiogenic properties. Its downregulation is associated with a worsened survival of breast carcinoma patients. Aim of this study was to analyze the CMG2 mRNA and protein expression in soft tissue sarcoma and their association with patient outcome. CMG2 mRNA was measured in 121 tumor samples of soft tissue sarcoma patients using quantitative real-time PCR. CMG2 protein was evaluated in 52 tumor samples by ELISA. CMG2 mRNA was significantly correlated with the corresponding CMG2 protein expression (r_s = 0.31; p = 0.027). CMG2 mRNA expression was associated with the mRNA expressions of several ECM and tissue remodeling enzymes, among them CD26 and components of the uPA system. Low CMG2 mRNA expression was correlated with a worsened patients' disease-specific survival in Kaplan-Meier analyses (mean patient survival was 25 vs. 96 months; p = 0.013), especially in high-stage tumors. A decreased CMG2 expression is a negative prognostic factor for soft tissue sarcoma patients. CMG2 may be an interesting candidate gene for the further exploration of soft tissue sarcoma genesis and progression.

Keywords: CMG2; outcome; pathobiology; soft tissue sarcoma.

Figure 1

Box-Plot overview on CMG2 mRNA expression in the different soft tissue sarcoma histological subtypes (a) and tumor stages (b). Numbers in bracket depict the cases (n) per category. Median CMG2 mRNA expression was slightly, but not significantly higher in leimosarcoma and NOS (a), and in stage 1 or stage 4 tumors (b). Abbreviations: LS—liposarcoma; FS—fibrosarcoma; RMS—rhabdomyosarcoma; LMS—leiomyosarcoma; NS—neuronal sarcoma; Syn—synovial sarcoma; NOS—not other specified.

Figure 2

Bivariate correlation analyses of CMG2 mRNA expression and CD26 mRNA (a), uPA mRNA (b), PAI-1 mRNA (c) and CMG2 protein (d) expression.

Figure 3

Survival analyses for CMG2 mRNA expression and protein expression in soft tissue sarcoma patients. Kaplan-Meier survival analyses revealed a significant worsened prognosis for patients with a low CMG2 mRNA expression in their tumors (a), but not for protein expression (c). Multivariate Cox’s regression analyses exhibited the detrimental effect of low CMG2 mRNA (b) and CMG2 protein (d) expression on patients’ disease-specific survival.

Figure 4

Comparative data on to the impact of CMG2 mRNA expression on the overall survival of breast (a), ovarian (b), lung (c), and gastric (d) cancer patients. Plots were drawn by the Kaplan-Meier Plotter algorithm (Available online: http://kmplot.com/analysis) facilitating microarray data of the CMG2/ANTXR2 probe 225524_at. Abbreviations: HR—hazard ratio.