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构建氧化应激基因特征以鉴定肺腺癌患者的亚型和预后。

Oxidative stress gene signature construction to identify subtypes and prognosis of patients with lung adenocarcinoma.

作者信息

Li Lan, Qin Rujia, Wang Xuefeng, Cao Ke, Lu Fei, Chen Zhengting, Gao Jingyan, Qiu Linbo, Shu Sisong, Lu Han, Chang Li, Li Wenhui

机构信息

Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Hospital/Peking University Cancer Hospital Yunnan, Kunming 650118, Yunnan, China.

Key Laboratory of Lung Cancer Research of Yunnan Province, The Third Affiliated Hospital of Kunming Medical University/Yunnan Cancer Center, Kunming 650118, Yunnan, China.

出版信息

Heliyon. 2024 Sep 24;10(20):e38306. doi: 10.1016/j.heliyon.2024.e38306. eCollection 2024 Oct 30.

Abstract

BACKGROUND

Although oxidative stress and malignancies are intimately connected, it is unknown how lung adenocarcinoma (LUAD) is affected by oxidative stress response-related genes (OSRGs).Our goal in this work was to create a genetic signature based on OSRGs that might both predict prognosis and hint to potential treatment options for LUAD.

METHODS

Clinicopathological and transcriptome information on LUAD patients was obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A model for predicting risk was created using LASSO regression. The TCGA, GSE72094, and GSE41271 cohorts all demonstrated the risk model's prediction ability. Immune cell infiltration was measured using the CIBERSORT method, and the TIDE platform was implemented to evaluate the therapeutic efficacy of immune checkpoint inhibition (ICI). Chemotherapy sensitivity was predicted using drug activity data by the Genomics of Drug Sensitivity. An investigation into gene expression was conducted using qRT-PCR. CCK-8 and transwell assays were employed to look into how DKK1 affected the migration and proliferation of LUAD cells.

RESULTS

A gene signature consisting of , , , , , , , and was efficiently determined and used to calculate a patient-specific risk score, this functioned as a stand-alone biomarker for prediction. Correlations were found between risk scores and immune cell infiltration frequency, ICI therapy response rate, estimated chemotherapeutic drug susceptibility and autophagy-related genes.Furthermore, DKK1 knockdown reduced the ability of LUAD cells to multiply and migrate.

CONCLUSION

Our thorough transcriptome study of OSRGs generated a biological framework effective in forecasting outcome and responsiveness to therapy in LUAD patients.

摘要

背景

尽管氧化应激与恶性肿瘤密切相关,但尚不清楚肺腺癌(LUAD)如何受到氧化应激反应相关基因(OSRGs)的影响。我们在这项工作中的目标是基于OSRGs创建一个基因特征,该特征既可以预测预后,又可以为LUAD的潜在治疗选择提供线索。

方法

从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)中获取LUAD患者的临床病理和转录组信息。使用LASSO回归创建了一个预测风险的模型。TCGA、GSE72094和GSE41271队列均证明了风险模型的预测能力。使用CIBERSORT方法测量免疫细胞浸润,并使用TIDE平台评估免疫检查点抑制(ICI)的治疗效果。通过药物敏感性基因组学利用药物活性数据预测化疗敏感性。使用qRT-PCR进行基因表达研究。采用CCK-8和transwell实验研究DKK1如何影响LUAD细胞的迁移和增殖。

结果

有效地确定了一个由 、 、 、 、 、 、 和 组成的基因特征,并用于计算患者特异性风险评分,该评分可作为独立的预测生物标志物。发现风险评分与免疫细胞浸润频率、ICI治疗反应率、估计的化疗药物敏感性和自噬相关基因之间存在相关性。此外,DKK1基因敲低降低了LUAD细胞的增殖和迁移能力。

结论

我们对OSRGs进行的全面转录组研究生成了一个有效的生物学框架,可用于预测LUAD患者的预后和治疗反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2486/11619975/4624cbd3e01c/gr1.jpg

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