Mining the prognostic significance and immune infiltration of STAT family members in human breast cancer by bioinformatics analysis.
Mining the prognostic significance and immune infiltration of STAT family members in human breast cancer by bioinformatics analysis.
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DOI：
10.21037/gs-22-189
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发表时间：
2021-01
期刊：
影响因子：
1.8
通讯作者：
Yudong Zhou;Siyuan Jiang;Shibo Yu;Lizhe Zhu;Yang Liu;Shou-zhi Li;N. Hao;Yu Ren
中科院分区：
文献类型：
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作者：
Yudong Zhou;Siyuan Jiang;Shibo Yu;Lizhe Zhu;Yang Liu;Shou-zhi Li;N. Hao;Yu Ren
研究背景越来越多的证据证明信号转导和转录激活因子（STAT）蛋白是细胞质内的转录因子，在许多细胞生物学过程中起关键作用，并可能是某些癌症的预后预测因子。然而，每个STAT家族成员在乳腺癌（BRCA）中的作用是多样的和有争议的。本研究旨在系统挖掘STAT家族成员在人类BRCA中的免疫浸润和预后意义。方法基于美国癌症基因组图谱（TCGA）数据库，应用Oncomine、基因表达谱交互分析（GEPIA）和人类蛋白质图谱分析STAT家族成员在正常乳腺和肿瘤组织中的表达。采用Kaplan-Meier Plotter、GEPIA和PrognoScan评估不同STAT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）分析和后续的功能富集分析。最后利用R 17软件的“ESTIMATE”和“ggcorrplot”包进行免疫浸润分析。结果STAT 2 [P<0.01，HR =1.23，95% CI：1.07-1.42]和STAT 3 [P=0.018，HR =0.69，95% CI：0.51-0.94]可作为预测总生存期的独立危险因素。基于GSE 19615（P=0.021，HR =0.21，95%CI：0.06-0.79）和GSE 2034（P=0.015，HR =0.57，95%CI：0.37-0.90）数据集，STAT 4可用作BRCA无远处转移生存期的独立预测因子。同时，STAT 5A、STAT 5 B和STAT 6也被证明可以独立预测BRCA的预后。此外，STAT 4共表达基因的功能机制主要集中在免疫相关通路，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STAT家族成员在BRCA中的表达与免疫浸润密切相关，并具有预后意义。结果表明，除STAT 1外，个体STATs可作为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。
Background Growing evidence proved that signal transducer and activators of transcription (STAT) 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 STAT family members in breast cancer (BRCA) is diverse and controversial. This study aimed to systematic mine the prognostic significance and immune infiltration of STAT 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 STAT 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 STATs 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 STAT2 [P<0.01, hazard ratio (HR) =1.23, 95% confidence interval (CI): 1.07-1.42] and STAT3 (P=0.018, HR =0.69, 95% CI: 0.51-0.94) could be an independent risk factor for predicting overall survival (OS). STAT4 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, STAT5A, STAT5B and STAT6 also have been shown to independently predict the prognosis of BRCA. Additionally, the functional mechanisms of STAT4 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 STAT family members in BRCA and their correlation with immune infiltration. The results suggest that individual STATs, except STAT1, may act as a prognostic biomarker for BRCA and provide a reference for further potential immunotherapies.