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通过单细胞RNA测序研究KARS在肺腺癌中的作用。

Investigating the role of KARS in lung adenocarcinoma via single-cell RNA sequencing.

作者信息

Hu Huafang, Zhong Yan, Li Guangbiao, Deng Ru, Lin Jingfu, Wu Wenkun, Li Yonghong

机构信息

Department of Radiology, Liuzhou Traditional Chinese Medicine Hospital, No. 6, Honghu Road, Liuzhou, 545001, Guangxi, China.

Department of Nursing, Liuzhou Traditional Chinese Medicine Hospital, No. 6, Honghu Road, Liuzhou, 545001, Guangxi, China.

出版信息

Discov Oncol. 2024 Dec 3;15(1):740. doi: 10.1007/s12672-024-01633-6.

Abstract

OBJECTIVE

Lung Adenocarcinoma (LUAD) is one of the leading causes to cancer-related deaths worldwide and exhibited extensive molecular diversity in its cellular components. In summary, this study examined the expression and function of KARS in various LUAD cell populations using single-cell RNA sequencing (scRNA-seq) to identify its prognostic value as well as potential implications for therapy.

METHODS

All datasets related to this study were analyzed in previous published studies, which was downloaded from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression(GTEx) project and Gene Expression Omnibus (GEO). We subsequently sought to analyze the association between either clinically tumorigenic or low survival-grade KARS expression, respectively with varied clinicopathological features and all patients OS. Verification of KARS expression was performed by in vitro RT-PCR.

RESULTS

Our investigation found that KARS expression was markedly elevated in LUAD tissue samples compared to normal controls. Genomic analysis indicated a robust association between increased copy number of the KARS gene and its overexpression. The upregulation of KARS was also correlated with distinct genetic mutations and a higher mutational load in LUAD. The heightened activity of KARS was implicated in LUAD progression. Furthermore, our research indicated a significant interplay between KARS's role in LUAD and the tumor's immune microenvironment, along with various dimensions of the tumor immunology landscape. Comprehensive assessments of immune cell populations within the tumor microenvironment uncovered a pronounced link between heightened immune responses and the presence of specific immune cell types. KARS expression in A549 cell line was higher than in the 16HBE cell line.

CONCLUSION

Utilizing single-cell omics technologies, this research offers a detailed perspective on the role of KARS in LUAD, highlighting its potential as a prognostic biomarker and a candidate for tailored therapeutic intervention. Future research should probe possible therapeutic strategies that could target KARS in a pathologically relevant manner.

摘要

目的

肺腺癌(LUAD)是全球癌症相关死亡的主要原因之一,其细胞成分表现出广泛的分子多样性。总之,本研究使用单细胞RNA测序(scRNA-seq)检测了KARS在各种LUAD细胞群体中的表达和功能,以确定其预后价值以及对治疗的潜在影响。

方法

本研究相关的所有数据集均来自先前发表的研究,从癌症基因组图谱(TCGA)、基因型-组织表达(GTEx)项目和基因表达综合数据库(GEO)下载。随后,我们试图分别分析临床致瘤性或低生存分级的KARS表达与不同临床病理特征及所有患者总生存期之间的关联。通过体外逆转录聚合酶链反应(RT-PCR)验证KARS的表达。

结果

我们的研究发现,与正常对照相比,LUAD组织样本中KARS表达明显升高。基因组分析表明,KARS基因拷贝数增加与其过表达之间存在密切关联。KARS的上调还与LUAD中不同的基因突变和更高的突变负荷相关。KARS活性增强与LUAD进展有关。此外,我们的研究表明KARS在LUAD中的作用与肿瘤免疫微环境以及肿瘤免疫格局的各个维度之间存在显著相互作用。对肿瘤微环境中免疫细胞群体的综合评估发现,免疫反应增强与特定免疫细胞类型的存在之间存在明显联系。A549细胞系中KARS的表达高于16HBE细胞系。

结论

本研究利用单细胞组学技术,详细阐述了KARS在LUAD中的作用,突出了其作为预后生物标志物和定制治疗干预候选物的潜力。未来的研究应探索以病理相关方式靶向KARS的可能治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/37a9/11615165/fc7567519641/12672_2024_1633_Fig1_HTML.jpg

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