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肺鳞状细胞癌的多种突变具有共同机制。

Multiple mutations of lung squamous cell carcinoma shared common mechanisms.

作者信息

Li Qianping, Hou Junyi, Hu Zhaoyan, Gu Biao, Shi Yan

机构信息

Department of Cardiothoracic Surgery, Shanghai University of Medicine & Health Sciences Shanghai Sixth People's Hospital East Campus, Shanghai, PR China.

Department of Gastroenterology, Shanghai University of Medicine & Health Sciences Shanghai Sixth People's Hospital East Campus, Shanghai, PR China.

出版信息

Oncotarget. 2016 Nov 29;7(48):79629-79636. doi: 10.18632/oncotarget.13190.

Abstract

Lung squamous cell carcinoma (LUSC) is a subtype of non-small cell lung cancers which is the cause of 80% of all lung cancer deaths. The genes that highly mutated in patients with LUSC and their roles played in the tumorigenesis remains unknown. Data of patients with Lung squamous cell carcinoma (LUSC) were retrieved from The Cancer Genome Atlas (TCGA). Differentially expressed genes were identified between control and cancer samples. Patients and controls can be separated by mRNA expression level showing that the between-group variance and totally 1265 genes were differentially expressed between controls and patients. Top genes whose mutations highly occurred in patients with LUSC were identified, most of these genes were shown to be related with tumorigenesis in previous studies. All of the genes mostly mutated were independently correlated with expression levels of all genes. These mutations did not show the trend of co-occurrence. However, the influenced gene of these mutations had overlaps. After studying the intersection of these genes, a group of shared genes were identified. The shared pathways enriched which played critical role in LUSC were identified based on these shared genes. Different mutations had contribution to the progression of LUSC. Though these genes involved different specific mechanisms, most of them may share a common mechanism which is critical for LUSC. The results may suggest a neglected mechanism and also indicate a potential target for therapies.

摘要

肺鳞状细胞癌(LUSC)是非小细胞肺癌的一种亚型,占所有肺癌死亡病例的80%。LUSC患者中高度突变的基因及其在肿瘤发生中的作用尚不清楚。从癌症基因组图谱(TCGA)中检索肺鳞状细胞癌(LUSC)患者的数据。在对照样本和癌症样本之间鉴定出差异表达基因。患者和对照可以通过mRNA表达水平进行区分,这表明组间差异以及共有1265个基因在对照和患者之间存在差异表达。鉴定出在LUSC患者中高度发生突变的顶级基因,其中大多数基因在先前的研究中已显示与肿瘤发生相关。所有大多数发生突变的基因均与所有基因的表达水平独立相关。这些突变未显示共发生趋势。然而,这些突变的受影响基因存在重叠。在研究这些基因的交集后,鉴定出一组共享基因。基于这些共享基因鉴定出在LUSC中起关键作用的富集的共享通路。不同的突变对LUSC的进展有贡献。尽管这些基因涉及不同的具体机制,但它们中的大多数可能共享一种对LUSC至关重要的共同机制。这些结果可能提示一种被忽视的机制,也指出了潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8303/5346741/7fe27b687d03/oncotarget-07-79629-g001.jpg

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