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解析肺腺癌中线粒体代谢相关基因的交替景观及其潜在机制。

Dissecting the alternation landscape of mitochondrial metabolism-related genes in lung adenocarcinoma and their latent mechanisms.

机构信息

Department of Thoracic Surgery, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, China.

Genecast Biotechnology, Wuxi, Jiangsu Province, China.

出版信息

Aging (Albany NY). 2023 Jun 15;15(12):5482-5496. doi: 10.18632/aging.204803.

Abstract

Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer with high incidence and unsatisfactory prognosis. The majority of LUAD patients eventually succumb to local and/or distinct metastatic recurrence. Genomic research of LUAD has broadened our understanding of this disease's biology and improved target therapies. However, the alternation landscape and characteristics of mitochondrial metabolism-related genes (MMRGs) in LUAD progression remain poorly understood. We performed a comprehensive analysis to identify the function and mechanism of MMRGs in LUAD based on the TCGA and GEO databases, which might offer therapeutic values for clinical researchers. Then, we figured out three hub prognosis-associated MMRGs (also termed as PMMRGs: ACOT11, ALDH2, and TXNRD1) that were engaged in the evolution of LUAD. To investigate the correlation between clinicopathological characteristics and MMRGs, we divided LUAD samples into two clusters (C1 and C2) based on key MMRGs. In addition, important pathways and the immune infiltration landscape affected by LUAD clusters were also delineated. Further, we nominated potential regulatory mechanisms underlying the MMRGs in LUAD development and progression. In conclusion, our integrative analysis enables a more comprehensive understanding of the mutation landscape of MMRGs in LUAD and provides an opportunity for more precise treatment.

摘要

肺腺癌(LUAD)是最常见的肺癌组织学亚型,发病率高,预后不佳。大多数 LUAD 患者最终死于局部和/或远处转移复发。LUAD 的基因组研究拓宽了我们对这种疾病生物学的理解,并改善了靶向治疗。然而,LUAD 进展中与线粒体代谢相关基因(MMRGs)的改变景观和特征仍知之甚少。我们基于 TCGA 和 GEO 数据库进行了全面分析,以确定 MMRGs 在 LUAD 中的功能和机制,这可能为临床研究人员提供治疗价值。然后,我们确定了三个与预后相关的关键 MMRGs(也称为 PMMRGs:ACOT11、ALDH2 和 TXNRD1),它们参与了 LUAD 的演变。为了研究 MMRGs 与临床病理特征之间的相关性,我们根据关键 MMRGs 将 LUAD 样本分为两个聚类(C1 和 C2)。此外,还描绘了受 LUAD 聚类影响的重要途径和免疫浸润景观。此外,我们提出了 LUAD 中 MMRGs 发展和进展背后的潜在调控机制。总之,我们的综合分析使我们能够更全面地了解 LUAD 中 MMRGs 的突变景观,并为更精确的治疗提供了机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8202/10333067/1b33f0281834/aging-15-204803-g001.jpg

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