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与免疫和氨基酸代谢相关的基因在肺腺癌中的预后及临床价值

The prognostic and clinical value of genes associate with immunity and amino acid Metabolism in Lung Adenocarcinoma.

作者信息

Zhang Yuxin, Wang Yuehui, Zhang Ruoxuan, Li Quanwang

机构信息

Beijing University of Chinese Medicine, No.11, North Third Ring East Road, Chaoyang District, Beijing, 100029, China.

Dongfang Hospital, Beijing University of Chinese Medicine, No. 6 fangxingyuan, Fengtai District, Beijing, 100078, China.

出版信息

Heliyon. 2024 Jun 6;10(12):e32341. doi: 10.1016/j.heliyon.2024.e32341. eCollection 2024 Jun 30.

DOI:10.1016/j.heliyon.2024.e32341
PMID:39183890
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11341317/
Abstract

BACKGROUND

Lung adenocarcinoma (LUAD) is the commonest subtype of primary lung cancer. A comprehensive analysis of the association of immunity with amino acid metabolism in LUAD is critical for understanding the disease.

METHODS

The present study examined LUAD and noncancerous cases from the TCGA database. Differentially expressed genes (DEGs) between LUAD and noncancerous tissues were detected by analyzing processed expression profiles. We cross-referenced the up-regulated DEGs with Immune and Amino Acid Metabolism-related genes (I&AAMGs), resulting in Immune and Amino Acid Metabolism related differentially expressed genes (IAAAMRDEGs). The STRING database was employed to analyze PPI on IAAAMRDEGs, obtaining excavated hub genes, whose biological processes, molecular functions and cellular components were examined with GO/KEGG. Potential mechanisms related to LUAD were investigated by GSEA and GSVA. A prognostic model was built by LASSO-COX analysis, taking into consideration risk scores and prognostic factors to determine biomarkers affecting LUAD occurrence and prognosis.

RESULTS

Totally 377 genes were detected at the intersection of upregulated DEGs and I&AAMGs. Analysis of PPI on these 377 IAAAMRDEGs yielded 17 hub genes. A LASSO regression analysis was utilized to assess the prognostic values of the 17 hub genes. Validation using the combined dataset confirmed 4 genes, e.g., polo-like kinase (PLK1), Ribonucleotide Reductase Subunit M2 (RRM2), Thyroid Hormone Receptor Interactor 13 (TRIP13), and Hyaluronan-Mediated Motility Receptor (HHMR). The model's accuracy was further assessed by ROC curve analysis and the COX model. In addition, immunohistochemical staining obtained from the HPA database, revealed enhanced PLK1 expression in LUAD samples.

CONCLUSION

LUAD pathogenesis is highly associated with immunity and amino acid metabolism. The PLK1, RRM2, TRIP13, and HMMR genes have prognostic values for LUAD. PLK1 upregulation in LUAD might be involved in tumorigenesis by modulating the cell cycle and represents a potential prognostic factor in clinic.

摘要

背景

肺腺癌（LUAD）是原发性肺癌最常见的亚型。全面分析LUAD中免疫与氨基酸代谢的关联对于理解该疾病至关重要。

方法

本研究检测了来自TCGA数据库的LUAD和非癌病例。通过分析处理后的表达谱来检测LUAD与非癌组织之间的差异表达基因（DEGs）。我们将上调的DEGs与免疫和氨基酸代谢相关基因（I&AAMGs）进行交叉引用，得到免疫和氨基酸代谢相关差异表达基因（IAAAMRDEGs）。利用STRING数据库分析IAAAMRDEGs上的蛋白质-蛋白质相互作用（PPI），获得挖掘出的枢纽基因，通过基因本体论（GO）/京都基因与基因组百科全书（KEGG）对其生物学过程、分子功能和细胞成分进行研究。通过基因集富集分析（GSEA）和基因集变异分析（GSVA）研究与LUAD相关的潜在机制。通过LASSO-COX分析建立预后模型，考虑风险评分和预后因素以确定影响LUAD发生和预后的生物标志物。

结果

在上调的DEGs与I&AAMGs的交集处共检测到377个基因。对这377个IAAAMRDEGs进行PPI分析产生了17个枢纽基因。利用LASSO回归分析评估这17个枢纽基因的预后价值。使用合并数据集进行验证确认了4个基因，即polo样激酶（PLK1）、核糖核苷酸还原酶亚基M2（RRM2）、甲状腺激素受体相互作用蛋白13（TRIP13）和透明质酸介导的运动受体（HHMR）。通过ROC曲线分析和COX模型进一步评估了该模型的准确性。此外，从人类蛋白质图谱（HPA）数据库获得的免疫组织化学染色显示LUAD样本中PLK1表达增强。

结论

LUAD的发病机制与免疫和氨基酸代谢高度相关。PLK1、RRM2、TRIP13和HMMR基因对LUAD具有预后价值。LUAD中PLK1的上调可能通过调节细胞周期参与肿瘤发生，并代表临床上一种潜在的预后因素。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bf/11341317/ca2fbb9c4605/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3bf/11341317/141e9ffbd0fb/gr8.jpg
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本文引用的文献

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HMMR associates with immune infiltrates and acts as a prognostic biomaker in lung adenocarcinoma.HMMR 与免疫浸润物相关，并作为肺腺癌的预后生物标志物。
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