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通过生物信息学分析挖掘人类乳腺癌中家族成员的预后意义和免疫浸润情况。

Mining the prognostic significance and immune infiltration of family members in human breast cancer by bioinformatics analysis.

作者信息

Zhou Yudong, Jiang Siyuan, Yu Shibo, Zhu Lizhe, Liu Yang, Li Shouyu, Hao Na, Ren Yu

机构信息

Department of Breast Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

出版信息

Gland Surg. 2022 Apr;11(4):720-741. doi: 10.21037/gs-22-189.

Abstract

BACKGROUND

Growing evidence proved that signal transducer and activators of transcription () proteins are cytoplasmic transcription factors known to play key roles in many cellular biological processes and may be prognostic predictors of some cancers. However, the role of each family members in breast cancer (BRCA) is diverse and controversial. This study aimed to systematic mine the prognostic significance and immune infiltration of family member in human BRCA.

METHODS

Based on The Cancer Genome Atlas (TCGA) database, we used the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and The Human Protein Atlas to analyze the expression of family members in normal human breast and tumor tissues. The Kaplan-Meier Plotter, GEPIA and PrognoScan were utilized to assess the prognostic value of different in BRCA. Then we used the cBioPortal, STRING, GeneMANIA and Metascape to make further mutation analysis, protein-protein interaction (PPI) analysis and subsequent functional enrichment analysis. Finally, the "ESTIMATE" and "ggcorrplot" package of R 17 software were used for immune infiltration analysis.

RESULTS

[P<0.01, hazard ratio (HR) =1.23, 95% confidence interval (CI): 1.07-1.42] and (P=0.018, HR =0.69, 95% CI: 0.51-0.94) could be an independent risk factor for predicting overall survival (OS). could be used as an independent predictor of distant metastasis-free survival in BRCA based on both GSE19615 (P=0.021, HR =0.21, 95% CI: 0.06-0.79) and GSE2034 (P=0.015, HR =0.57, 95% CI: 0.37-0.90) datasets. Meanwhile, , and also have been shown to independently predict the prognosis of BRCA. Additionally, the functional mechanisms of co-expressed genes were mainly focused on immune-related pathways and its expression was associated with immune checkpoint-associated genes and immunomodulators in BRCA.

CONCLUSIONS

Our study mined the prognostic significance of family members in BRCA and their correlation with immune infiltration. The results suggest that individual , except , may act as a prognostic biomarker for BRCA and provide a reference for further potential immunotherapies.

摘要

背景

越来越多的证据表明,信号转导和转录激活因子()蛋白是细胞质转录因子,已知在许多细胞生物学过程中起关键作用,并且可能是某些癌症的预后预测指标。然而,每个家族成员在乳腺癌(BRCA)中的作用是多样且存在争议的。本研究旨在系统挖掘家族成员在人类BRCA中的预后意义和免疫浸润情况。

方法

基于癌症基因组图谱(TCGA)数据库,我们使用Oncomine、基因表达谱交互式分析(GEPIA)和人类蛋白质图谱来分析家族成员在正常人类乳腺和肿瘤组织中的表达。利用Kaplan-Meier Plotter、GEPIA和PrognoScan评估不同在BRCA中的预后价值。然后我们使用cBioPortal、STRING、GeneMANIA和Metascape进行进一步的突变分析、蛋白质-蛋白质相互作用(PPI)分析以及后续的功能富集分析。最后,使用R 17软件的“ESTIMATE”和“ggcorrplot”包进行免疫浸润分析。

结果

[P<0.01,风险比(HR)=1.23,95%置信区间(CI):1.07 - 1.42]和(P = 0.018,HR = 0.69,95% CI:0.51 - 0.94)可能是预测总生存期(OS)的独立危险因素。基于GSE19615(P = 0.021,HR = 0.21,95% CI:0.06 - 0.79)和GSE2034(P = 0.015,HR = 0.57,95% CI:0.37 - 0.90)数据集,可作为BRCA远处无转移生存期的独立预测指标。同时,、和也已被证明可独立预测BRCA的预后。此外,共表达基因的功能机制主要集中在免疫相关途径,并且其表达与BRCA中的免疫检查点相关基因和免疫调节剂相关。

结论

我们的研究挖掘了家族成员在BRCA中的预后意义及其与免疫浸润的相关性。结果表明,除了之外,个体可能作为BRCA的预后生物标志物,并为进一步的潜在免疫治疗提供参考。

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