Trop2 is overexpressed in gastric cancer and predicts poor prognosis

Abstract

The cell surface protein Trop2 is overexpressed in a variety of human cancers. Trop2 expression increases tumor development and metastasis and reduces patient survival. However, little is known about the role of Trop2 expression and its prognostic value in gastric cancer (GC), particularly in Chinese populations. We analyzed Trop2 expression in GC tissues collected from Chinese GC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry on tissue microarrays were performed to assess levels of Trop2 mRNA and protein in GC, and correlations between Trop2 expression and clinical characteristics and prognosis were analyzed. Trop2 expression was higher in GC tissues than in neighboring non-tumor tissues. Increased Trop2 protein levels in GC were associated with increased differentiation, tumor node metastasis stage, tumor size, lymph node metastasis, distant metastasis, and H. pylori infection. GC patients with high Trop2 expression also had poor overall survival rates. These data suggest Trop2 is a useful prognostic biomarker for GC.

Keywords: Trop2; gastric cancer; prognosis.

Figure 1. Trop2 mRNA expression in 41 GC tissue pairs

Trop2 mRNA expression was examined by qRT-PCR and normalized to β-actin. Trop2 mRNA levels were higher in the 41 GC tissues (T) than in matched tumor neighbor tissues (N) (**p < 0.001).

Figure 2. Representative images of Trop2 protein expression in gastric tissue TMA sections

(A) Middle differentiated gastric cancer with high Trop2 expression (IHC score, 300); (B) Poor differentiated gastric cancer with high Trop2 expression (IHC score, 270); (C) Signet ring cell gastric cancer with low Trop2 expression (IHC score, 60); (D) Matched tumor neighbor tissues with low Trop2 expression (IHC score, 30); (E) Chronic gastritis with low Trop2 expression (IHC score, 30); (F) Intestinal metaplasia with high Trop2 expression (IHC score, 260); (G) Low-grade intraepithelial neoplasia with low Trop2 expression (IHC score, 30); (H) High-grade intraepithelial neoplasia with low Trop2 expression (IHC score, 60); Row 1 and 3 are Trop2 staining with × 4 (bar = 500 μm), Row 2 and 4 are Trop2 staining with × 40 (bar = 50 μm).

Figure 3. Survival curves for gastric cancer using the Kaplan-Meier method and the log-rank test

(A); a Overall survival curves for patients with low or no Trop2 expression (blue line, 1) and patients with high Trop2 expression of (green line, 2); b disease-free survival curves for patients with low or no Trop2 expression (blue line, 1) and high Trop2 expression (green line, 2). (B) Overall survival curves by TNM stage; TNM 0 (blue line, 1), TNM Ia and Ib (green line, 2), TNM IIa and IIb (grey line, 3), TNM IIIa and IIIb (purple line, 4), TNM IIIc and IV (yellow line, 5). (C) overall survival curves for H. pylori negative (blue line, 1) and positive (green line, 2) patients.