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泛癌分析揭示SOX2是包括胰腺癌在内的多种癌症类型中一种有前景的预后和免疫治疗生物标志物。

Pan-Cancer Analysis Reveals SOX2 as a Promising Prognostic and Immunotherapeutic Biomarker Across Various Cancer Types, Including Pancreatic Cancer.

作者信息

Ding Yuntao, Wang Huizhi, Wang Qiaowei, Jiang Han, Li Zhangzuo, Yu Zhengyue, Wang Qi, Xu Min

机构信息

Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, China.

Hematological Disease Institute of Jiangsu University, Affiliated Hospital of Jiangsu University, Jiangsu University, Zhenjiang, 212001, China.

出版信息

J Cancer. 2024 Jan 1;15(1):251-274. doi: 10.7150/jca.88397. eCollection 2024.

DOI:10.7150/jca.88397
PMID:38164286
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10751676/
Abstract

SOX2 is associated with the initiation, growth, and progression of various tumors and is related to stem cells. However, further studies of SOX2 in a pan-cancer context are warranted. In this study, we obtained pan-cancer and clinical data from TCGA, GTEx, STRING, and TISIDB databases and we analyzed the relationship between SOX2 expression levels and changes in gene diagnostics and survival prognosis. Additionally, we compared the expression levels of SOX2 in pancreatic cancer and healthy pancreatic tissues using Wilcoxon's rank-sum test. Functional enrichment analysis was conducted to identify potential signaling pathways and biological functions. To determine the prognostic value, we used the area under the curve (AUC) and Cox regression analysis. We further developed nomograms to predict overall survival at 1, 6, and 12 months after cancer diagnosis. Moreover, we assessed immune cell infiltration using single-sample gene set enrichment analysis. The methylation status of SOX2 was analyzed using the UALCAN and MethSurv databases. Furthermore, we verified the differential expression of SOX2 in pancreatic cancer cell lines by western blotting and quantitative polymerase chain reaction. We also confirmed the effect of SOX2 on the invasion and migration of pancreatic cancer cells using transwell and scratch assays. The biological effects were confirmed using a clone-formation assay. Our findings suggest that SOX2 is highly expressed in various tumor tissues and has potential clinical significance. It can be used as a new biomarker for pancreatic adenocarcinoma and plays a crucial role in immune infiltration.

摘要

SOX2与多种肿瘤的发生、生长和进展相关,且与干细胞有关。然而,有必要在泛癌背景下对SOX2进行进一步研究。在本研究中,我们从TCGA、GTEx、STRING和TISIDB数据库获取了泛癌和临床数据,并分析了SOX2表达水平与基因诊断及生存预后变化之间的关系。此外,我们使用Wilcoxon秩和检验比较了胰腺癌组织和健康胰腺组织中SOX2的表达水平。进行功能富集分析以确定潜在的信号通路和生物学功能。为了确定预后价值,我们使用了曲线下面积(AUC)和Cox回归分析。我们进一步绘制了列线图以预测癌症诊断后1、6和12个月的总生存率。此外,我们使用单样本基因集富集分析评估了免疫细胞浸润情况。使用UALCAN和MethSurv数据库分析了SOX2的甲基化状态。此外,我们通过蛋白质免疫印迹法和定量聚合酶链反应验证了SOX2在胰腺癌细胞系中的差异表达。我们还使用Transwell和划痕实验证实了SOX2对胰腺癌细胞侵袭和迁移的影响。使用克隆形成实验证实了其生物学效应。我们的研究结果表明,SOX2在各种肿瘤组织中高表达,具有潜在的临床意义。它可作为胰腺腺癌的一种新的生物标志物,并在免疫浸润中起关键作用。

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