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核受体相互作用蛋白1(NRIP1)在胃腺癌中的表达及作用

Expression and role of nuclear receptor-interacting protein 1 (NRIP1) in stomach adenocarcinoma.

作者信息

Fang Dalang, Lu Guanming

机构信息

Department of Glandular Surgery, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.

出版信息

Ann Transl Med. 2020 Oct;8(20):1293. doi: 10.21037/atm-20-6197.

Abstract

BACKGROUND

Nuclear receptor-interacting protein 1 (NRIP1), also named NR140, has been observed differentially express in multiple cancers, but the expression levels and the prognostic role of NRIP1 in stomach adenocarcinoma (STAD) remain unclear.

METHODS

We used the Gene Expression Profiling Interactive Analysis (GEPIA) to analyze the NRIP1 expression levels in STAD, subgroups analysis of expression of NRIP1 via the UALCAN dataset. Further, cBioPortal was used to investigate the aberration type, co-mutations status, and located mutation of NRIP1. Correlated genes, and kinases, microRNA (miRNA), and transcription factor (TF) targets were identified using LinkedOmics. The Kaplan-Meier (K-M) plotter was used to analyze the prognosis of NRIP1 and the significantly correlated genes in STAD. Then, the tumor immune estimation resource (Timer) was used to explore the relation between NRIP1 and the immune cell infiltration, and the role of immune cells in STAD. The Human Protein Atlas (HPA) was used to confirm the NRIP1 protein express in STAD stomach tissue and normal stomach tissue.

RESULTS

NRIP1 significantly overexpress in STAD, and the NRIP1 expression levels were impacted by clinical features. Overexpression of NRIP1 indicated the poor prognosis of STAD. Functional enrichment analysis showed the NRIP1 mainly enriched in immune response-regulating signaling pathway, cell-substrate adhesion, mRNA processing, and pathway in cancer. Overexpression USP25, SNYJ1 indicated the poor outcome of STAD, but the overexpression of BACH1 indicated protective biomarker. MIR-331 and MIR-132 have important role in STAD. Further, NRIP1 had a significant relation with immune infiltrates and other defined genes that significantly impact immune infiltrates. Immunohistochemical showed NRIP1 protein was higher in STAD than normal sample.

CONCLUSIONS

In this study, we revealed that overexpression of NRIP1 in the STAD sample compared to normal samples, NRIP1 significantly associated with macrophage. The high expression levels of NRIP1 and more macrophage infiltration led to poor prognosis of STAD.

摘要

背景

核受体相互作用蛋白1(NRIP1),也称为NR140,已被观察到在多种癌症中差异表达,但NRIP1在胃腺癌(STAD)中的表达水平和预后作用仍不清楚。

方法

我们使用基因表达谱交互式分析(GEPIA)来分析STAD中NRIP1的表达水平,通过UALCAN数据集对NRIP1的表达进行亚组分析。此外,使用cBioPortal研究NRIP1的畸变类型、共突变状态和定位突变。使用LinkedOmics鉴定相关基因、激酶、微小RNA(miRNA)和转录因子(TF)靶点。使用Kaplan-Meier(K-M)绘图仪分析NRIP1和STAD中显著相关基因的预后。然后,使用肿瘤免疫评估资源(Timer)探索NRIP1与免疫细胞浸润之间的关系,以及免疫细胞在STAD中的作用。使用人类蛋白质图谱(HPA)确认NRIP1蛋白在STAD胃组织和正常胃组织中的表达。

结果

NRIP1在STAD中显著过表达,且NRIP1表达水平受临床特征影响。NRIP1的过表达表明STAD预后不良。功能富集分析表明,NRIP1主要富集于免疫反应调节信号通路、细胞-基质粘附、mRNA加工和癌症通路。USP25、SNYJ1的过表达表明STAD预后不良,但BACH1的过表达表明其为保护性生物标志物。MIR-331和MIR-132在STAD中起重要作用。此外,NRIP1与免疫浸润以及其他显著影响免疫浸润的特定基因有显著关系。免疫组织化学显示,STAD中NRIP1蛋白高于正常样本。

结论

在本研究中,我们发现与正常样本相比,STAD样本中NRIP1过表达,NRIP1与巨噬细胞显著相关。NRIP1的高表达水平和更多的巨噬细胞浸润导致STAD预后不良。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f88e/7661897/23f73d895f00/atm-08-20-1293-f1.jpg

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