Background: Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide. Synaptophysin-like 2 (SYPL2) is a neuroendocrine-related protein highly expressed in skeletal muscle and the tongue. The involvement of SYPL2 in CRC, including its level of expression and function, has not been evaluated.
Aim: To evaluate the correlations of SYPL2 expression with lymph node metastasis (LNM) and prognosis in patients with CRC.
Methods: The levels of expression of SYPL2 in CRC and normal colorectal tissues were analyzed in multiple public and online databases. The associations between clinical variables and SYPL2 expression were evaluated statistically, and the associations between SYPL2 expression and prognosis in patients with CRC were analyzed using the Kaplan-Meier method and univariate/multivariate Cox regression analyses. SYPL2 expression was assessed in 20 paired CRC tissue and adjacent normal colorectal tissue samples obtained from Fuyang People's Hospital, and the associations between SYPL2 expression and the clinical characteristics of these patients were investigated. Correlations between the levels of expression of SYPL2 and key targeted genes were determined by Pearson's correlation analysis. The distribution of immune cells in these samples was calculated using the CIBERSORT algorithm. Gene set enrichment analysis (GSEA) was performed to evaluate the biofunction and pathways of SYPL2 in CRC.
Results: SYPL2 expression was significantly lower in CRC tissue samples than in normal colorectal tissue samples (P < 0.05). High SYPL2 levels in CRC tissues correlated significantly with LNM (P < 0.05) and a poorer patient prognosis, including significantly shorter overall survival (OS) [hazard ratio (HR) = 1.9, P < 0.05] and disease-free survival (HR = 1.6, P < 0.05). High SYPL2 expression was an independent risk factor for OS in both univariate (HR = 2.078, P = 0.014) and multivariate (HR = 1.754, P = 0.018) Cox regression analyses. In addition, SYPL2 expression correlated significantly with the expression of KDR (P < 0.0001, r = 0.47) and the BRAF V600E mutation (P < 0.05). Higher SYPL2 expression was associated with the enrichment of CD8 T-cells and M0 macrophages in the tumor microenvironment. GSEA revealed that SYPL2 was associated with the regulation of epithelial cell migration, vasculature development, pathways in cancer, and several vital tumor-related pathways.
Conclusion: SYPL2 expression was lower in CRC tissue than in normal colorectal tissue. Higher SYPL2 expression in CRC was significantly associated with LNM and poorer survival.
Keywords: Bevacizumab; Colorectal cancer; Immune microenvironment; Lymph node metastasis; Prognosis; Synaptophysin-like 2.
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