A Signature Constructed Based on the Integrin Family Predicts Prognosis and Correlates with the Tumor Microenvironment of Patients with Lung Adenocarcinoma.

Shusen Zhang, Dengxiang Liu, Xuecong Ning, Xiaochong Zhang, Yuanyuan Lu, Yang Zhang, Aimin Li, Zhiguo Gao, Zhihua Wang, Xiaoling Zhao, Shubo Chen, Zhigang Cai
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Abstract

As an important element in regulating the tumor microenvironment (TME), integrin plays a key role in tumor progression. This study aimed to establish prognostic signatures to predict the overall survival and identify the immune landscape of patients with lung adenocarcinoma based on integrins. The Cancer Genome Atlas-Lung Adenocarcinoma (TCGA-LUAD) and Gene Expression Omnibus datasets were used to obtain information on mRNA levels and clinical factors (GSE72094). The least absolute shrinkage and selection operator (LASSO) model was used to create a prediction model that included six integrin genes. The nomogram, risk score, and time-dependent receiver operating characteristic analysis all revealed that the signatures had a good prognostic value. The gene signatures may be linked to carcinogenesis and TME, according to a gene set enrichment analysis. The immunological and stromal scores were computed using the ESTIMATE algorithm, and the data revealed, the low-risk group had a higher score. We discovered that the B lymphocytes, plasma, CD4+ T, dendritic, and mast cells were much higher in the group with low-risk using the CiberSort. Inflammatory processes and several HLA family genes were upregulated in the low-risk group. The low-risk group with a better prognosis is more sensitive to immune checkpoint inhibitor medication, according to immunophenoscore (IPS) research. We found that the patients in the high-risk group were more susceptible to chemotherapy than other group patients, according to the prophetic algorithm. The gene signatures could accurately predict the prognosis, identify the immune status of patients with lung adenocarcinoma, and provide guidance for therapy.

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基于整合素家族构建的特征预测肺腺癌患者预后及与肿瘤微环境相关
作为调控肿瘤微环境(tumor microenvironment, TME)的重要元件,整合素在肿瘤的进展中起着关键作用。本研究旨在建立基于整合素的肺腺癌患者的预后特征,以预测总体生存和识别免疫景观。使用癌症基因组图谱-肺腺癌(TCGA-LUAD)和基因表达Omnibus数据集获取mRNA水平和临床因素的信息(GSE72094)。采用最小绝对收缩和选择算子(LASSO)模型建立了包含6个整合素基因的预测模型。nomogram, risk score, and time-dependent receiver operating characteristic analysis均显示这些特征具有良好的预后价值。根据一项基因集富集分析,这些基因特征可能与致癌和TME有关。使用ESTIMATE算法计算免疫和间质评分,数据显示,低风险组得分较高。我们发现B淋巴细胞、血浆、CD4+ T、树突状细胞和肥大细胞在使用CiberSort的低风险组中要高得多。炎症过程和几个HLA家族基因在低危组上调。根据免疫表型评分(IPS)的研究,预后较好的低风险组对免疫检查点抑制剂药物更敏感。我们发现,根据预测算法,高危组患者比其他组患者更容易接受化疗。基因标记可以准确预测预后,识别肺腺癌患者的免疫状态,为治疗提供指导。
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来源期刊
CiteScore
3.80
自引率
0.00%
发文量
20
审稿时长
>12 weeks
期刊介绍: The Journal of Environmental Pathology, Toxicology and Oncology publishes original research and reviews of factors and conditions that affect human and animal carcinogensis. Scientists in various fields of biological research, such as toxicologists, chemists, immunologists, pharmacologists, oncologists, pneumologists, and industrial technologists, will find this journal useful in their research on the interface between the environment, humans, and animals.
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