Published online Nov 15, 2022. doi: 10.4251/wjgo.v14.i11.2122
Peer-review started: July 4, 2022
First decision: August 13, 2022
Revised: August 24, 2022
Accepted: October 11, 2022
Article in press: October 11, 2022
Published online: November 15, 2022
Processing time: 133 Days and 20.7 Hours
Colorectal cancer (CRC) is the third-most common cause of cancer deaths worldwide and lymph node metastasis (LNM) is important in CRC staging and patient prognosis. Risk factors for LNM include lymphovascular invasion, histological grade, submucosal invasion depth, and tumor budding. In addition, LNM of CRC is usually evaluated by radiologic methods, including computed tomography, magnetic resonance imaging etc. However, these imaging methods cannot accurately evaluate LNM. It was necessary to investigate key biomarkers to predict LNM and prognosis in patients with CRC. Moreover, synaptophysin-like 2 (SYPL2) is a neuroendocrine-related cytosolic protein enriched primarily in skeletal muscles and the tongue. The role of SYPL2 in cancer, including CRC, has not been determined.
The role of SYPL2 in CRC has not been studied. The present study comprehensively and systematically compared SYPL2 expression and potential functions. The relationship between SYPL2 expression and clinicopathological characteristics was completed. And we found that high expression of SYPL2 was significantly associated with LNM and worse prognosis. And we verified the results by experiment. In addition, we analyzed the correlation between SYPL2 expression and the expression and mutation of target genes.
This study aimed to investigate the SYPL2 expression, potential biological functions and pathways, correlation clinicopathological characteristics and prognosis in CRC.
The gene expression profiles and associated clinicopathological data of patients with CRC were downloaded from multiple public and online databases {The Cancer Genome Atlas, GEO, Gene Expression Profiling Interactive Analysis [gene set enrichment analysis (GSEA)]}. The associations between clinical variables, prognosis and SYPL2 expression were analyzed statistically using the Kaplan-Meier method, univariate/multivariate Cox regression analyses, chi-squared and Fisher’s exact tests. In addition, we collected 20 paired CRC tissue and adjacent normal colorectal tissue samples for validation by quantitative real-time polymerase chain reaction (qRT-PCR). GSEA was performed to evaluate the biofunction and pathways of SYPL2 in CRC.
SYPL2 expression was significantly lower in CRC tissue samples than in normal colorectal tissue samples. High SYPL2 levels in CRC tissues correlated significantly with LNM and worse prognosis. High SYPL2 expression was an independent risk factor for overall survival in both univariate and multivariate Cox regression analyses. SYPL2 expression correlated significantly with the expression of KDR and high SYPL2 expression was correlate with the response to bevacizumab treatment. Higher SYPL2 expression was associated with the enrichment of CD8 T-cells and M0 macrophages. GSEA revealed that SYPL2 was associated with the regulation of epithelial cell migration, vasculature development, pathways in cancer, and several vital tumor-related pathways.
SYPL2 expression was lower in CRC than in adjacent normal tissue. However, high SYPL2 expression was significantly associated with lymph node metastases and poorer survival.
The SYPL2 gene expression and the correlations between clinical variables, prognosis were analyzed by multiple public and online databases. Furthermore, we collected 20 paired CRC tissue and adjacent normal colorectal tissue samples for validation by qRT-PCR.