Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2022; 14(11): 2122-2137
Published online Nov 15, 2022. doi: 10.4251/wjgo.v14.i11.2122
Synaptophysin-like 2 expression correlates with lymph node metastasis and poor prognosis in colorectal cancer patients
Zong-Xian Zhao, Qin-Lingfei Liu, Yao Yuan, Fu-Sheng Wang
Zong-Xian Zhao, Yao Yuan, Fu-Sheng Wang, Department of Anorectal Surgery, Fuyang People’s Hospital, Fuyang 236000, Anhui Province, China
Qin-Lingfei Liu, Department of Digestive Internal Medicine, Tianjin Medical University General Hospital, Tianjin 300070, China
Author contributions: Zhao ZX and Liu QL collected data and completed the manuscript; Yuan Y collected relevant reference and completed a part of experiment; Wang FS designed the study and assisted in writing the manuscript; and all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved for publication by our Institutional Reviewer.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at 461901580@qq.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zong-Xian Zhao, MD, Researcher, Surgeon, Department of Anorectal Surgery, Fuyang People’s Hospital, No. 501 Sanqing Road, Yingzhou District, Fuyang 236000, Anhui Province, China. 461901590@qq.com
Received: July 4, 2022
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
Abstract
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 BRAFV600E 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: Synaptophysin-like 2; Colorectal cancer; Lymph node metastasis; Prognosis; Immune microenvironment; Bevacizumab

Core Tip: In this research, we reported the expression and biofunctions of synaptophysin-like 2 (SYPL2) in colorectal cancer (CRC) for the first time. SYPL2 correlated with lymph node metastasis and a poor prognosis (both overall and disease-free survival) in CRC. SYPL2 mainly influence CD8 T-cell and M0 macrophage enrichment in the tumor microenvironment. Gene set enrichment analysis indicated that SYPL2 might also influence the tumor vasculature development. In addition, we found that SYPL2 was correlated with the effect of bevacizumab therapy.