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利用 XTABLE 研究肺鳞癌通路功能障碍的癌前演变

Interrogating the precancerous evolution of pathway dysfunction in lung squamous cell carcinoma using XTABLE.

机构信息

Cancer Biomarker Centre, Cancer Research UK Manchester Institute, The University of Manchester, Macclesfield, United Kingdom.

Cancer Research UK Lung Cancer Centre of Excellence, Alderley Park, United Kingdom.

出版信息

Elife. 2023 Mar 9;12:e77507. doi: 10.7554/eLife.77507.

Abstract

Lung squamous cell carcinoma (LUSC) is a type of lung cancer with a dismal prognosis that lacks adequate therapies and actionable targets. This disease is characterized by a sequence of low- and high-grade preinvasive stages with increasing probability of malignant progression. Increasing our knowledge about the biology of these premalignant lesions (PMLs) is necessary to design new methods of early detection and prevention, and to identify the molecular processes that are key for malignant progression. To facilitate this research, we have designed XTABLE (Eploring rnscriptomes of ronchial esions), an open-source application that integrates the most extensive transcriptomic databases of PMLs published so far. With this tool, users can stratify samples using multiple parameters and interrogate PML biology in multiple manners, such as two- and multiple-group comparisons, interrogation of genes of interests, and transcriptional signatures. Using XTABLE, we have carried out a comparative study of the potential role of chromosomal instability scores as biomarkers of PML progression and mapped the onset of the most relevant LUSC pathways to the sequence of LUSC developmental stages. XTABLE will critically facilitate new research for the identification of early detection biomarkers and acquire a better understanding of the LUSC precancerous stages.

摘要

肺鳞状细胞癌(LUSC)是一种预后不良的肺癌,缺乏有效的治疗方法和可行的靶点。这种疾病的特征是一系列低级别和高级别癌前阶段,恶性进展的概率逐渐增加。为了设计新的早期检测和预防方法,并确定促进恶性进展的关键分子过程,我们有必要深入了解这些癌前病变(PMLs)的生物学特性。为了促进这项研究,我们设计了 XTABLE(支气管病变转录组学探索),这是一个开源应用程序,集成了迄今为止发表的最广泛的 PML 转录组数据库。使用这个工具,用户可以使用多个参数对样本进行分层,并以多种方式研究 PML 生物学,例如进行两组和多组比较、研究感兴趣的基因,以及转录特征分析。使用 XTABLE,我们进行了一项关于染色体不稳定性评分作为 PML 进展生物标志物的潜在作用的比较研究,并将最相关的 LUSC 通路的起始与 LUSC 发育阶段的顺序进行了映射。XTABLE 将极大地促进早期检测生物标志物的识别,并深入了解 LUSC 癌前阶段。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d860/10038660/a6d2cb7c5b21/elife-77507-fig1.jpg

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