Overexpression of LBX2 associated with tumor progression and poor prognosis in colorectal cancer

Colorectal cancer (CRC) is one of the most common carcinomas with high morbidity and mortality worldwide. However, the underlying molecular mechanisms of CRC are unclear. The aim of the present study was to establish the role that overexpression of LBX2 serves in CRC and to investigate the associated biological pathways. The difference in the expression levels of LBX2 between CRC tissues and adjacent normal colorectal tissues was assessed using the Oncomine database and Tumor Immune Estimation Resource. The expression levels of LBX2 and its prognostic significance in CRC were analyzed using a t-test and χ(2) test using data from The Cancer Genome Atlas database. The Kaplan-Meier method and Cox regression analysis were used to estimate the prognostic value of LBX2 in CRC. Furthermore, the potential mechanisms of LBX2 dysregulation and its underlying molecular mechanisms in CRC were investigated using Gene Set Enrichment Analysis (GSEA). LBX2 expression levels were significantly upregulated in CRC samples compared with corresponding normal colorectal tissues (P<0.05). LBX2 upregulation was correlated with advanced tumor stage (III or IV), vascular invasion, lymphatic invasion and the male sex (all P<0.05). Kaplan-Meier analyses showed that high expression levels of LBX2 were associated with a less favorable overall survival (OS) and disease-free survival (DFS) in CRC (all P<0.05). Multivariate analyses further confirmed that LBX2 upregulation was an independent indicator of less favorable OS and DFS (all P<0.05). In addition, LBX2 DNA hypomethylation and microRNA (miR)-378a-3p downregulation correlated with LBX2 upregulation in CRC (all P<0.05). The downregulation of miR-378a-3p in CRC was also significantly associated with less favorable OS and DFS, as demonstrated using Kaplan-Meier analyses (all P<0.05). Moreover, GSEA indicated that ‘VEGF signaling’, ‘Cell adhesion molecules CAMs’, ‘Toll-like receptor signaling’ and ‘Natural killer cell-mediated cytotoxicity’ signaling pathways were enriched in the high LBX2 expressing cohort (all P<0.05). Thus, overexpression of LBX2 may be associated with the development of CRC and may serve as a novel prognostic marker and therapeutic target in CRC. The mechanisms of LBX2 upregulation in CRC are possibly associated with LBX2 DNA hypomethylation and miR-378a-3p downregulation. The potential mechanisms of LBX2 upregulation in CRC might be regulated via the ‘Cell adhesion molecules CAMs’, ‘Toll-like receptor signaling’ and ‘Natural killer cell-mediated cytotoxicity’ signaling pathways.