IMP3 Is a Novel Prognostic Marker that Correlates with Colon Cancer Progression and Pathogenesis

Abstract

Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) plays a vital role in carcinogenesis; however, its significance and prognostic value in colon cancer remain unclear. In this study, a tissue microarray (TMA) containing 203 samples of primary colon cancer was assessed for IMP3 expression by immunohistochemistry. The TMA included 66 lymph node metastasis (LNM) samples. The mRNA and protein expression levels of IMP3 were evaluated by reverse transcription-PCR and Western blot analysis, respectively. Cytoplasmic immunoreactivity of IMP3 was significantly higher in LNM (93%) than in primary colon cancer (65%) or normal mucosa (3.9%). Increased IMP3 levels were significantly correlated with higher clinical stage, T classification, LNM, presence of distant metastasis, and Ki-67 positivity. IMP3 was up-regulated in colon cancer compared with paired normal colonic mucosa. IMP3 expression was associated with an 11-fold increased risk of distant metastases (hazard ratio (HR) 10.7; 95% confidence interval (CI) 3.3-34.5; P < 0.0001). Patients with IMP3-positive localized tumors had lower 5-year disease-free survival (DFS) (HR 2.87; 95% CI 1.65-4.98; P < 0.0001) and overall survival (OS) (HR 4.2; 95% CI 2.51-10.17; P < 0.0001) than those with IMP3-negative tumors. Multivariate survival analysis showed that IMP3 was an independent prognostic marker for DFS (HR 1.92; 95% CI 1.06-3.47; P = 0.03) and OS (HR 2.37; 95% CI 1.2-4.7; P = 0.014). IMP3 may play an important role in colon cancer progression and could serve as a prognostic biomarker to identify patients at risk of developing metastasis or recurrence after colonectomy.