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高STK40表达作为低级别胶质瘤的独立预后生物标志物并与免疫浸润相关

High STK40 Expression as an Independent Prognostic Biomarker and Correlated with Immune Infiltrates in Low-Grade Gliomas.

作者信息

Pan Heyue, Liu Qirui, Zhang Fuchi, Wang Xiaohua, Wang Shouyong, Shi Xiangsong

机构信息

Department of Neurology, The Third People's Hospital of Huai'an, Huai'an, Jiangsu, 223001, People's Republic of China.

Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People's Republic of China.

出版信息

Int J Gen Med. 2021 Oct 5;14:6389-6400. doi: 10.2147/IJGM.S335821. eCollection 2021.

DOI:10.2147/IJGM.S335821
PMID:34675607
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8502031/
Abstract

BACKGROUND

Expression of STK40 is observed in some cancer types, while its role in low-grade gliomas (LGG) is unclear. The present study aimed to demonstrate the relationship between STK40 and LGG based on The Cancer Genome Atlas (TCGA) database and bioinformatics analysis.

METHODS

Kruskal-Wallis test, Wilcoxon sign-rank test, and logistic regression were used to evaluate the relationship between clinicopathological features and STK40 expression. Kaplan-Meier method and Cox regression analysis were used to evaluate prognostic factors. Gene set enrichment analysis (GSEA) and immuno-infiltration analysis were used to determine the significant involvement of STK40 in function.

RESULTS

High STK40 expression in LGG was associated with WHO grade (P<0.001), IDH status (P<0.001), primary therapy outcome (P=0.027), 1p/19q codeletion (P<0.001) and histological type (P<0.001). High STK40 expression predicted a poorer overall survival (OS) (HR: 3.07; 95% CI: 2.09-4.51; P<0.001), progression-free survival (PFS) (HR:2.11; 95% CI: 1.59-2.81; P<0.001) and disease specific survival (DSS) (HR: 3.27; 95% CI: 2.17-4.92; P<0.001). STK40 expression (HR: 2.284; 95% CI: 1.125-4.637; P=0.022) was independently correlated with OS in LGG patients. GSEA demonstrated that pathways including cell cycle mitotic, neutrophil degranulation, signaling by Rho GTPases, signaling by interleukins, M phase, PI3K-Akt signaling pathway and naba secreted factors were differentially enriched in STK40 high expression phenotype. Immune infiltration analysis showed that STK40 expression was correlated with some types of immune infiltrating cells.

CONCLUSION

STK40 expression was significantly correlated with poor survival and immune infiltration in LGG, and it may be a promising prognostic biomarker in LGG.

摘要

背景

在某些癌症类型中观察到STK40的表达,但其在低级别胶质瘤(LGG)中的作用尚不清楚。本研究旨在基于癌症基因组图谱(TCGA)数据库和生物信息学分析来阐明STK40与LGG之间的关系。

方法

采用Kruskal-Wallis检验、Wilcoxon符号秩检验和逻辑回归来评估临床病理特征与STK40表达之间的关系。采用Kaplan-Meier法和Cox回归分析来评估预后因素。基因集富集分析(GSEA)和免疫浸润分析用于确定STK40在功能上的显著参与情况。

结果

LGG中STK40的高表达与世界卫生组织(WHO)分级(P<0.001)、异柠檬酸脱氢酶(IDH)状态(P<0.001)、初始治疗结果(P=0.027)、1p/19q共缺失(P<0.001)和组织学类型(P<0.001)相关。STK40的高表达预示着较差的总生存期(OS)(风险比[HR]:3.07;95%置信区间[CI]:2.09 - 4.51;P<0.001)、无进展生存期(PFS)(HR:2.11;95% CI:1.59 - 2.81;P<0.001)和疾病特异性生存期(DSS)(HR:3.27;95% CI:2.17 - 4.92;P<0.001)。STK40表达(HR:2.284;95% CI:1.125 - 4.637;P=0.022)与LGG患者的OS独立相关。GSEA表明,包括细胞周期有丝分裂、中性粒细胞脱颗粒、Rho GTP酶信号传导、白细胞介素信号传导、M期、PI3K - Akt信号通路和纳巴分泌因子等通路在STK40高表达表型中差异富集。免疫浸润分析表明,STK40表达与某些类型的免疫浸润细胞相关。

结论

STK40表达与LGG的不良生存和免疫浸润显著相关,它可能是LGG中一个有前景的预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/b26f92dbfe91/IJGM-14-6389-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/fad86b82d0d8/IJGM-14-6389-g0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/6db226c73f19/IJGM-14-6389-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/b26f92dbfe91/IJGM-14-6389-g0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/fad86b82d0d8/IJGM-14-6389-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/17dc919f6862/IJGM-14-6389-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/071a5763a0cb/IJGM-14-6389-g0003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5f6/8502031/b26f92dbfe91/IJGM-14-6389-g0007.jpg

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