Anoikis-related gene signatures can aid prognosis of lung adenocarcinoma.

IF 2.1 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Guiyan Mo, Xuan Long, Zan Hu, Yuling Tang, Zhiguo Zhou
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引用次数: 0

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer, and while advancements in diagnosis, surgery, radiotherapy, and molecular therapy have improved clinical prognosis, the long-term survival rate and quality of life of patients remain unsatisfactory. Therefore, identifying new prognostic biomarkers and potential therapeutic targets is crucial.

Objectives: This study aimed to analyze the role of anoikis-related gene characteristics in LUAD.

Material and methods: The anoikis-related genes were obtained from the GeneCards database. Genetic expression data and clinical characteristic information were collected from The Cancer Genome Atlas (TCGA)-LUAD, and the Gene Expression Omnibus (GEO) GSE31210, GSE37745, and GSE68465 datasets. Random survival forest and least absolute shrinkage and selection operator (LASSO) models were applied to construct the risk model. An analysis of immune cell infiltration and function was performed with the scores.

Results: Four prognosis-related genes (TLE1, GLI2, PLK1, and BAK1) were obtained and used to construct the anoikis score. We found that the patient survival rate was higher in the low-anoikis score (LAS) group. Moreover, both the stromal and immune scores were negatively correlated with the anoikis score. With the increase of the anoikis score, the levels of natural killer cells, regulatory T cells, CD4+ T cells, CD8+ T cells, B cells, and macrophages decreased. The anoikis score had a negative regulatory relationship with the immune response, natural killer cell activation and T cell activation. The TP53 mutation was significant in LUAD patients and was present in 56% of the high-anoikis score (HAS) group and in 40% of the LAS group.

Conclusions: The anoikis score was associated with poor prognosis in LUAD patients. Anoikis-related genes were associated with tumor immune dysregulation and TP53 mutation in LUAD. This study opens a new perspective for LUAD therapy.

失巢相关基因特征可以帮助肺腺癌的预后。
背景:肺腺癌(LUAD)是癌症最常见的亚型,尽管诊断、手术、放疗和分子治疗的进步改善了临床预后,但患者的长期生存率和生活质量仍不令人满意。因此,识别新的预后生物标志物和潜在的治疗靶点至关重要。目的:本研究旨在分析失巢相关基因特征在LUAD中的作用。材料和方法:从GeneCards数据库中获得失巢相关基因。从癌症基因组图谱(TCGA)-LUAD和基因表达综合(GEO)GSE31210、GSE37745和GSE68465数据集收集基因表达数据和临床特征信息。采用随机生存森林和最小绝对收缩选择算子(LASSO)模型构建风险模型。用评分对免疫细胞浸润和功能进行分析。结果:获得了四个预后相关基因(TLE1、GLI2、PLK1和BAK1),并用于构建失巢细胞评分。我们发现,低失巢综合征评分(LAS)组的患者生存率较高。此外,基质细胞和免疫评分均与失巢细胞评分呈负相关。随着anoikis评分的增加,自然杀伤细胞、调节性T细胞、CD4+T细胞、CD8+T细胞,B细胞和巨噬细胞的水平降低。anoikis评分与免疫反应、自然杀伤细胞活化和T细胞活化呈负调控关系。TP53突变在LUAD患者中具有显著性,在高失巢细胞评分(HAS)组和LAS组中分别有56%和40%存在。结论:失巢细胞积分与LUAD患者预后不良有关。失巢相关基因与LUAD中的肿瘤免疫失调和TP53突变有关。这项研究为LUAD的治疗开辟了一个新的视角。
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来源期刊
Advances in Clinical and Experimental Medicine
Advances in Clinical and Experimental Medicine MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
3.70
自引率
4.80%
发文量
153
审稿时长
6-12 weeks
期刊介绍: Advances in Clinical and Experimental Medicine has been published by the Wroclaw Medical University since 1992. Establishing the medical journal was the idea of Prof. Bogumił Halawa, Chair of the Department of Cardiology, and was fully supported by the Rector of Wroclaw Medical University, Prof. Zbigniew Knapik. Prof. Halawa was also the first editor-in-chief, between 1992-1997. The journal, then entitled "Postępy Medycyny Klinicznej i Doświadczalnej", appeared quarterly. Prof. Leszek Paradowski was editor-in-chief from 1997-1999. In 1998 he initiated alterations in the profile and cover design of the journal which were accepted by the Editorial Board. The title was changed to Advances in Clinical and Experimental Medicine. Articles in English were welcomed. A number of outstanding representatives of medical science from Poland and abroad were invited to participate in the newly established International Editorial Staff. Prof. Antonina Harłozińska-Szmyrka was editor-in-chief in years 2000-2005, in years 2006-2007 once again prof. Leszek Paradowski and prof. Maria Podolak-Dawidziak was editor-in-chief in years 2008-2016. Since 2017 the editor-in chief is prof. Maciej Bagłaj. Since July 2005, original papers have been published only in English. Case reports are no longer accepted. The manuscripts are reviewed by two independent reviewers and a statistical reviewer, and English texts are proofread by a native speaker. The journal has been indexed in several databases: Scopus, Ulrich’sTM International Periodicals Directory, Index Copernicus and since 2007 in Thomson Reuters databases: Science Citation Index Expanded i Journal Citation Reports/Science Edition. In 2010 the journal obtained Impact Factor which is now 1.179 pts. Articles published in the journal are worth 15 points among Polish journals according to the Polish Committee for Scientific Research and 169.43 points according to the Index Copernicus. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been indexed and included in National Library of Medicine’s MEDLINE database. English abstracts printed in the journal are included and searchable using PubMed http://www.ncbi.nlm.nih.gov/pubmed.
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