Protein Disulfide-Isomerase A3 Is a Robust Prognostic Biomarker for Cancers and Predicts the Immunotherapy Response Effectively.
Protein Disulfide-Isomerase A3 Is a Robust Prognostic Biomarker for Cancers and Predicts the Immunotherapy Response Effectively.
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DOI：
10.3389/fimmu.2022.837512
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发表时间：
2022
影响因子：
7.3
通讯作者：
Huang K
中科院分区：
文献类型：
--
作者：
Tu Z;Ouyang Q;Long X;Wu L;Li J;Zhu X;Huang K
蛋白质二硫异构酶A3 （PDIA3）是蛋白质二硫异构酶（PDI）家族的成员，通过其蛋白质二硫异构酶功能参与蛋白质折叠。据报道，它可以调节几种癌症的进展，但其在癌症免疫治疗中的功能尚不清楚。从癌症基因组图谱（TCGA）和基因型-组织表达（GTEx）数据库中下载癌组织和正常组织的RNA-seq数据。使用Cbioportal数据集探索泛癌症中PDIA3的基因组改变信息。利用人类蛋白图谱（Human Protein Atlas， HPA）和ComPPI网站挖掘PDIA3蛋白信息，采用western blot法监测临床GBM样品中PDIA3表达上调情况。采用单因素Cox回归和Kaplan-Meier法评价PDIA3在泛癌中的预后作用。基因集富集分析（GSEA）用于寻找与PDIA3表达相关的癌症标志。TIMER2.0是研究泛癌中PDIA3相关免疫细胞浸润的主要平台。PDIA3与免疫治疗生物标志物之间的相关性采用Spearman相关分析。免疫印迹法定量PDIA3表达水平，集落形成法和transwell法检测胶质瘤细胞的增殖和侵袭能力。PDIA3在大多数癌症类型中过表达，在多种癌症中具有预测预后的能力，尤其是在恶性细胞和单核/巨噬细胞中表达。此外，PDIA3与免疫激活标志物、肿瘤免疫细胞浸润和免疫调节因子显著相关，最有趣的发现是PDIA3可以显著预测抗pdl1治疗反应。此外，我们还利用Connectivity Map （CMap）技术筛选了不同癌症类型中与PDIA3表达相关的特异性抑制剂。最后，PDIA3基因敲低可显著削弱胶质瘤细胞的增殖和侵袭能力。结果显示PDIA3是一种强大的肿瘤生物标志物。它在蛋白质二硫键调控中的作用可以影响蛋白质的合成、降解和分泌，从而塑造肿瘤微环境，这可能进一步应用于开发新的抗癌抑制剂。
Protein disulfide isomerase A3 (PDIA3) is a member of the protein disulfide isomerase (PDI) family that participates in protein folding through its protein disulfide isomerase function. It has been reported to regulate the progression of several cancers, but its function in cancer immunotherapy is unknown. The RNA-seq data of cancer and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. The Cbioportal dataset was used to explore the genomic alteration information of PDIA3 in pan-cancer. Human Protein Atlas (HPA) and ComPPI websites were employed to mine the protein information of PDIA3, and western blot assay was performed to monitor the upregulated PDIA3 expression in clinical GBM samples. The univariate Cox regression and the Kaplan–Meier method were utilized to appraise the prognostic role of PDIA3 in pan-cancer. Gene Set Enrichment Analysis (GSEA) was applied to search the associated cancer hallmarks with PDIA3 expression. TIMER2.0 was the main platform to investigate the immune cell infiltrations related to PDIA3 in pan-cancer. The associations between PDIA3 and immunotherapy biomarkers were performed by Spearman correlation analysis. The immunoblot was used to quantify the PDIA3 expression levels, and the proliferative and invasive ability of glioma cells was determined by colony formation and transwell assays. PDIA3 is overexpressed in most cancer types and exhibits prognosis predictive ability in various cancers, and it is especially expressed in the malignant cells and monocytes/macrophages. In addition, PDIA3 is significantly correlated with immune-activated hallmarks, cancer immune cell infiltrations, and immunoregulators, and the most interesting finding is that PDIA3 could significantly predict anti-PDL1 therapy response. Besides, specific inhibitors that correlated with PDIA3 expression in different cancer types were also screened by using Connectivity Map (CMap). Finally, knockdown of PDIA3 significantly weakened the proliferative and invasive ability of glioma cells. The results revealed that PDIA3 acts as a robust tumor biomarker. Its function in protein disulfide linkage regulation could influence protein synthesis, degradation, and secretion, and then shapes the tumor microenvironment, which might be further applied to develop novel anticancer inhibitors.
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影响因子：
10.1
作者：
Gabrilovich DI
通讯作者：
Gabrilovich DI
影响因子：
28.2
作者：
Dominguez, Claudia X.;Mueller, Soren;Turley, Shannon J.
通讯作者：
Turley, Shannon J.
DOI：
10.1074/jbc.m808054200
发表时间：
2009-01-23
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jessop CE;Tavender TJ;Watkins RH;Chambers JE;Bulleid NJ
通讯作者：
Bulleid NJ
影响因子：
64.5
作者：
Malta TM;Sokolov A;Gentles AJ;Burzykowski T;Poisson L;Weinstein JN;Kamińska B;Huelsken J;Omberg L;Gevaert O;Colaprico A;Czerwińska P;Mazurek S;Mishra L;Heyn H;Krasnitz A;Godwin AK;Lazar AJ;Cancer Genome Atlas Research Network;Stuart JM;Hoadley KA;Laird PW;Noushmehr H;Wiznerowicz M
通讯作者：
Wiznerowicz M
影响因子：
2.8
作者：
Koong, Luke Y.;Watson, Cheryl S.
通讯作者：
Watson, Cheryl S.