TBL1XR1 predicts isolated tumor cells and micrometastasis in patients with TNM stage I/II colorectal cancer

Abstract

BACKGROUND AND AIM: A considerable number of early-stage colorectal cancer (CRC) patients may develop cancer relapse or metastasis after curative surgery. Isolated tumor cells (ITC) and micrometastasis in lymph nodes (LNMM), which are undetectable by conventional pathological examination, may be one primary reason. Detection of ITC/LNMM is time-consuming and cost-ineffective; we aimed to find biomarkers in primary CRC tissues to help predicting ITC/LNMM status. METHODS: We enrolled 137 node-negative patients with early-stage CRC in this study. Existence of ITC/LNMM was identified by immunohistological staining with cytokeratin 20 in resected lymph nodes. Expression of transducin (β)-like 1 X-linked receptor 1 (TBL1XR1) in primary CRC tissues was also investigated. Chi-squared test was performed to reveal the correlations between ITC/LNMM and clinicopathological characteristics. Univariate and multivariate analyses were used to determine independent prognostic factors. Knockdown experiment together with proliferation and invasion assays were carried out to explore molecular mechanisms between TBL1XR1 and ITC/LNMM. RESULTS: About 29.2% (40/137) patients were identified as ITC/LNMM positive, and most of them (32/40 cases, 80%) showed high TBL1XR1 expression in primary CRC tissues. Both ITC/LNMM and TBL1XR1 expression were independent prognostic factors for disease relapse or metastasis. In vitro experiments demonstrated that TBL1XR1 can regulate the expression of vascular endothelial growth factor C and epithelial-mesenchymal transition proteins, thus mediate the process of lymph node metastasis. CONCLUSIONS: Identification of ITC/LNMM is significant in evaluating clinical outcome and guiding adjuvant chemotherapy for early-stage CRC patients. TBL1XR1 overexpression in CRC tissues can serve as an efficient biomarker to predict the status of ITC/LNMM.