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RUNX蛋白家族的泛癌图谱揭示了它们作为致癌生物标志物的潜力及其作用机制。

Pan-cancer Landscape of the RUNX Protein Family Reveals their Potential as Carcinogenic Biomarkers and the Mechanisms Underlying their Action.

作者信息

Pan Shen, Sun Siyu, Liu Bitian, Hou Yang

机构信息

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.

出版信息

J Transl Int Med. 2022 Jul 10;10(2):156-174. doi: 10.2478/jtim-2022-0013. eCollection 2022 Jun.

Abstract

BACKGROUND

The RUNX family of transcription factors plays an important regulatory role in tumor development. Although the importance of RUNX in certain cancer types is well known, the pan-cancer landscape remains unclear.

MATERIALS AND METHODS

Data from The Cancer Genome Atlas (TCGA) provides a pan-cancer overview of the genes. Hence, herein, we performed a pan-cancer analysis of abnormal expression and deciphered the potential regulatory mechanism. Specifically, we used TCGA multi-omics data combined with multiple online tools to analyze transcripts, genetic alterations, DNA methylation, clinical prognoses, miRNA networks, and potential target genes.

RESULTS

genes are consistently overexpressed in esophageal, gastric, pancreatic, and pan-renal cancers. The total protein expression of in lung adenocarcinoma, kidney renal clear cell carcinoma (KIRC), and uterine corpus endometrial carcinoma (UCEC) is consistent with the mRNA expression results. Moreover, increased phosphorylation on the T14 and T18 residues of RUNX1 may represent potential pathogenic factors. The genes are significantly associated with survival in pan-renal cancer, brain lower-grade glioma, and uveal melanoma. Meanwhile, various mutations and posttranscriptional changes, including the D96 mutation in invasive breast carcinoma, the co-occurrence of gene mutations in UCEC, and methylation changes in the promoter in KIRC, may be associated with cancer development. Finally, analysis of epigenetic regulator co-expression, miRNA networks, and target genes revealed the carcinogenicity, abnormal expression, and direct regulation of genes.

CONCLUSIONS

We successfully analyzed the pan-cancer abnormal expression and prognostic value of genes, thereby providing potential biomarkers for various cancers. Further, mutations revealed via genetic alteration analysis may serve as a basis for personalized patient therapies.

摘要

背景

转录因子RUNX家族在肿瘤发展中发挥重要调节作用。尽管RUNX在某些癌症类型中的重要性已为人所知,但泛癌情况仍不清楚。

材料与方法

来自癌症基因组图谱(TCGA)的数据提供了这些基因的泛癌概述。因此,在此我们对异常表达进行了泛癌分析,并解读了潜在的调控机制。具体而言,我们使用TCGA多组学数据结合多个在线工具来分析转录本、基因改变、DNA甲基化、临床预后、miRNA网络和潜在靶基因。

结果

这些基因在食管癌、胃癌、胰腺癌和全肾癌中持续过表达。在肺腺癌、肾透明细胞癌(KIRC)和子宫内膜癌(UCEC)中,其总蛋白表达与mRNA表达结果一致。此外,RUNX1的T14和T18残基磷酸化增加可能代表潜在致病因素。这些基因在全肾癌、脑低级别胶质瘤和葡萄膜黑色素瘤中与生存显著相关。同时,各种突变和转录后变化,包括浸润性乳腺癌中的D96突变、UCEC中基因突变的共发生以及KIRC中该基因启动子的甲基化变化,可能与癌症发展有关。最后,对表观遗传调节因子共表达、miRNA网络和靶基因的分析揭示了这些基因的致癌性、异常表达和直接调控。

结论

我们成功分析了这些基因的泛癌异常表达和预后价值,从而为各种癌症提供了潜在的生物标志物。此外,通过基因改变分析揭示的突变可能作为患者个性化治疗的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1231/9328034/9db2aa0c3984/jtim-10-156-g001.jpg

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