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SFRP基因家族成员在结直肠癌中的表达、预后、免疫浸润及DNA甲基化：一项比较生物信息学与实验分析

Expression, prognosis, immunological infiltration, and DNA methylation of members of the SFRP gene family in colorectal cancer: a comparative bioinformatic and experimental analysis.

作者信息

Yang Haicheng, Han Zhuo, Yang Ying, Zhou Shuai, Zhang Bo, He Jiaxing, He Xianli, Wang Nan

机构信息

Department of General Surgery, Tangdu Hospital, The Air Force Medical University, Xi'an, 710038, China.

出版信息

In Vitro Cell Dev Biol Anim. 2025 Feb;61(2):149-164. doi: 10.1007/s11626-024-00998-w. Epub 2024 Dec 27.

DOI:10.1007/s11626-024-00998-w
PMID:39729237
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11865182/
Abstract

This study aimed to investigate the expression, prognostic significance, methylation, and immune invasion levels of secreted frizzled-related proteins (SFRP1-5) in colorectal cancer (CRC). Additionally, the relationship between SFRP1/2 methylation and immune infiltration in CRC was explored. The expression of SFRP1-5 was analyzed using several databases, including GEO, TCGA, TIMER, STRING, and GEPIA. Molecular interactions with SFRPs were examined via Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes, and Genomes (KEGG) pathway analyses were conducted using the DAVID database. Methylation levels of SFRP1/2 in CRC were assessed through methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) experiments. Apoptosis and proliferation in CRC cells following the knockdown of SFRP1/2 expression were evaluated using flow cytometry and CCK-8 assays. The TISIDB database was used to analyze the relationship between SFRP1/2 methylation levels and immune infiltration. The expression of SFRP1, SFRP2, and SFRP5 was significantly lower in CRC patients, while SFRP4 expression was higher compared to that in healthy individuals. Elevated mRNA expression of SFRP2 was significantly associated with improved overall survival (OS), disease-specific survival, and progression-free intervals. SFRP1/2 expression was also linked to immune invasion, with higher levels correlating with increased immune infiltration. Both SFRP1 and SFRP2 showed hypermethylation in CRC. Knockdown of SFRP1/2 expression resulted in increased proliferation of CRC cells, and their methylation levels were inversely correlated with immune cell presence. The expression, methylation, and immune cell infiltration patterns of the SFRP family in CRC differed markedly from those in healthy individuals. These findings suggest that SFRPs may serve as potential therapeutic targets and key genes associated with immune cell infiltration in CRC.

摘要

本研究旨在探讨分泌型卷曲相关蛋白（SFRP1 - 5）在结直肠癌（CRC）中的表达、预后意义、甲基化及免疫浸润水平。此外，还探究了CRC中SFRP1/2甲基化与免疫浸润之间的关系。利用包括GEO、TCGA、TIMER、STRING和GEPIA在内的多个数据库分析SFRP1 - 5的表达。通过Cytoscape软件检测与SFRPs的分子相互作用。使用DAVID数据库进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路分析。通过甲基化特异性PCR（MSP）和亚硫酸氢盐测序PCR（BSP）实验评估CRC中SFRP1/2的甲基化水平。采用流式细胞术和CCK - 8检测评估SFRP1/2表达敲低后CRC细胞的凋亡和增殖情况。使用TISIDB数据库分析SFRP1/2甲基化水平与免疫浸润之间的关系。CRC患者中SFRP1、SFRP2和SFRP5的表达显著低于健康个体，而SFRP4的表达则高于健康个体。SFRP2的mRNA表达升高与总生存期（OS）、疾病特异性生存期和无进展生存期的改善显著相关。SFRP1/2的表达也与免疫浸润有关，水平越高，免疫浸润增加越明显。SFRP1和SFRP2在CRC中均表现为高甲基化。SFRP1/2表达的敲低导致CRC细胞增殖增加，其甲基化水平与免疫细胞的存在呈负相关CRC中SFRP家族的表达、甲基化和免疫细胞浸润模式与健康个体明显不同。这些发现表明，SFRPs可能作为潜在的治疗靶点以及与CRC中免疫细胞浸润相关的关键基因。

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SFRP4 Is a Potential Biomarker for the Prognosis and Immunotherapy for Gastric Cancer.分泌型卷曲相关蛋白4是胃癌预后及免疫治疗的潜在生物标志物。
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Potential genetic biomarker of Saudi Arabian patients with colorectal cancer.
沙特阿拉伯结直肠癌患者的潜在遗传生物标志物。
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The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection.早发性结直肠癌的上升趋势：流行病学、临床特征、生物学、危险因素、预防及早期检测的综合综述
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Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling.下调 SFRP2 通过激活 Wnt/β-catenin 信号通路促进胶质瘤细胞的癌症干性和放射抵抗性。
PLoS One. 2021 Dec 1;16(12):e0260864. doi: 10.1371/journal.pone.0260864. eCollection 2021.
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