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GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in pancreatic cancer.
Bioscience Reports ( IF 4 ) Pub Date : 2020-09-16 , DOI: 10.1042/bsr20202150
Hongkai Zhuang 1 , Chuanzhao Zhang 1 , Baohua Hou 1
Affiliation  

General Transcription Factor II-I Repeat Domain-Containing Protein 1 (GTF2IRD1) is a member of the GTF21 gene family, which encodes a set of multifunctional transcription factors. However, the potential function of GTF2IRD1 in pancreatic cancer (PC) still remains unknown. Study on GTF2IRD1 might provide a new insight into the carcinogenesis and therapeutics of PC. &#160;Methods: In the current study, the clinical significance and potential biological of GTF2IRD1 were evaluated by bioinformatics analysis. The oncogenic role of GTF2IRD1 in PC was also determined using in vitro studies. Possible associations between GTF2IRD1 expression and tumor immunity were analyzed using ESTIMATE algorithm and single sample Gene Set Enrichment Analysis (ssGSEA).</p> &#160;Results: GTF2IRD1 expression was significantly upregulated in tumor tissues, and positively associated with higher histologic grade, higher American Joint Committee on Cancer (AJCC) stage, and worse prognosis. Function enrichment analysis demonstrated that GTF2IRD1 may be involved in pancreatic adenocarcinoma pathway, TGF-β signaling pathway, and tumor-infiltrating lymphocyte (TIL) related biological functions, such as T cell receptor signaling pathway, leukocyte transendothelial migration, resistin as a regulator of inflammation, and regulation of leukocyte mediated cytotoxicity. Knockdown of GTF2IRD1 expression inhibited cancer cell proliferation, colony formation, and invasion in vitro. ESTIMATE algorithm and ssGSEA demonstrated that GTF2IRD1 expression negatively correlated with the infiltration and anti-tumor activity of TILs, especially for CD8+ T cells.</p> &#160;Conclusion: The study demonstrates that GTF2IRD1 overexpression promotes tumor progression and correlates with less CD8+ T cells infiltration in PC.

中文翻译:

GTF2IRD1过表达促进胰腺癌的进展并与较少的CD8 + T细胞浸润相关。

通用转录因子II-1重复域包含蛋白1(GTF2IRD1)是GTF21基因家族的成员,该家族编码一组多功能转录因子。但是,GTF2IRD1在胰腺癌(PC)中的潜在功能仍然未知。GTF2IRD1的研究可能为PC的致癌作用和治疗方法提供新的见解。&#160;方法:在本研究中,通过生物信息学分析评估了GTF2IRD1的临床意义和潜在生物学特性。还使用体外研究确定了GTF2IRD1在PC中的致癌作用。使用ESTIMATE算法和单样本基因集富集分析(ssGSEA)分析了GTF2IRD1表达与肿瘤免疫之间的可能关联。</ p>&#160;结果:肿瘤组织中GTF2IRD1表达显着上调,与较高的组织学等级,较高的美国癌症联合委员会(AJCC)分期和预后不良呈正相关。功能富集分析表明,GTF2IRD1可能参与了胰腺腺癌途径,TGF-β信号途径以及与肿瘤浸润淋巴细胞(TIL)相关的生物学功能,例如T细胞受体信号途径,白细胞跨内皮迁移,抵抗素作为炎症调节因子,并调节白细胞介导的细胞毒性。抑制GTF2IRD1表达可抑制癌细胞增殖,集落形成和体外侵袭。ESTIMATE算法和ssGSEA证明GTF2IRD1表达与TIL的浸润和抗肿瘤活性呈负相关,尤其是对于CD8 + T细胞。</ p>&#160;结论:
更新日期:2020-09-18
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