Prediction of prognosis and immune response in lung adenocarcinoma based on mitophagy and lactate-related gene signatures.

IF 2.4 3区 医学 Q3 ONCOLOGY
Wenjie Jiang, Fan Zhang, Zhen Tang, Shuonan Xu, Yukun Zhang, Lina Liu, Daixing Zhong, Yingxiang Liu
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Abstract

Background: Lung adenocarcinoma (LUAD) causes leading death worldwide. Mitophagy and lactate metabolism accumulation are distinctive features of LUAD. We aimed to identify lactate-related genes (LRGs) signatures based on mitophagy for predicting prognosis and immune response in LUAD.

Methods: The gene expression and clinical data were downloaded from TCGA and GEO database. First, the subtype analysis was analyzed based on 29 mitophagy genes. Survival, immune, and function differences between the different subtypes were analyzed. Then, based on mitophagy genes and 14 LRGs, the best LRGs were screened to construct a risk score model and combined with clinical factors to establish a nomogram for predicting patient survival. Finally, the expression level and molecular function of the key candidate gene OGDH were verified by in vitro experiments.

Results: All the LUAD samples were divided into 2 subtypes: sub1 and sub2. The sub2 possessed worse survival. Immune score, immune checkpoint genes, and human leucocyte antigen genes in sub1 were higher than in sub2. Six optimal mitophagy-related LRGs were used to construct a risk score model. A high-risk score indicates poorer survival, higher tumor mutation burden, and higher drug sensitivity. The nomogram was robust in predicting LUAD survival. The experiments in vitro showed that knockdown of OGDH inhibited the proliferation, migration and invasion in LUAD cells.

Conclusions: A nomogram based on the construction of the mitophagy-related lactate genes predicts prognosis and immune response in LUAD. These results could help with risk stratification and targeted therapy for LUAD.

基于丝裂吞噬和乳酸相关基因特征预测肺腺癌的预后和免疫反应
背景:肺腺癌(LUAD)是导致全球死亡的主要原因。有丝分裂和乳酸代谢积累是肺腺癌的显著特征。我们旨在基于有丝分裂鉴定乳酸相关基因(LRGs)特征,以预测LUAD的预后和免疫反应:方法:从TCGA和GEO数据库下载基因表达和临床数据。首先,基于29个有丝分裂基因进行亚型分析。首先,根据29个有丝分裂基因对亚型进行了分析,分析了不同亚型之间的生存、免疫和功能差异。然后,基于有丝分裂基因和14个LRGs,筛选出最佳LRGs构建风险评分模型,并与临床因素相结合,建立预测患者生存率的提名图。最后,通过体外实验验证了关键候选基因OGDH的表达水平和分子功能:结果:所有LUAD样本被分为两个亚型:sub1和sub2。结果:所有LUAD样本被分为2个亚型:亚1型和亚2型,亚2型的生存率更低。sub1亚型的免疫评分、免疫检查点基因和人类白细胞抗原基因高于sub2亚型。六个最佳有丝分裂相关 LRG 被用来构建风险评分模型。高风险评分表明生存率较低、肿瘤突变负荷较高和药物敏感性较高。该提名图在预测LUAD生存率方面非常稳健。体外实验表明,敲除OGDH可抑制LUAD细胞的增殖、迁移和侵袭:结论:基于有丝分裂相关乳酸基因构建的提名图可以预测 LUAD 的预后和免疫反应。这些结果有助于LUAD的风险分层和靶向治疗。
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来源期刊
CiteScore
6.80
自引率
3.00%
发文量
175
审稿时长
2 months
期刊介绍: The International Journal of Clinical Oncology (IJCO) welcomes original research papers on all aspects of clinical oncology that report the results of novel and timely investigations. Reports on clinical trials are encouraged. Experimental studies will also be accepted if they have obvious relevance to clinical oncology. Membership in the Japan Society of Clinical Oncology is not a prerequisite for submission to the journal. Papers are received on the understanding that: their contents have not been published in whole or in part elsewhere; that they are subject to peer review by at least two referees and the Editors, and to editorial revision of the language and contents; and that the Editors are responsible for their acceptance, rejection, and order of publication.
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