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NUAK1在胃腺癌中的预后意义及其与免疫浸润的关系

Prognostic significance of NUAK1 and its association with immune infiltration in stomach adenocarcinoma.

作者信息

Ni Xin, Pan Fan, Lang Ya Kun, Zhang Wei

机构信息

Department of Gastroenterology, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, Jiangsu, China.

Department of Articular Surgery, Affiliated Hospital of Jiangsu University, No. 438 Jiefang Road, Zhenjiang, Jiangsu, China.

出版信息

Discov Oncol. 2024 Dec 18;15(1):800. doi: 10.1007/s12672-024-01688-5.

Abstract

BACKGROUND

Stomach adenocarcinoma (STAD) represents a significant global health burden, accounting for a considerable proportion of cancer-related mortalities, and NUAK1, a protein kinase, plays a crucial role in cellular metabolism, cell cycle regulation, migration, and tumor progression. However, its relationship with prognosis and immune infiltration in STAD has not been thoroughly investigated.

METHODS

RNA sequencing data from the Cancer Genome Atlas (TCGA) and Genotypic Tissue Expression Project (GTEx) databases were employed to assess disparities in NUAK1 expression between STAD tumour and normal tissues. Additionally, we investigated the correlation between NUAK1 expression and patient prognosis, in addition to the level of immune cell infiltration. The potential functions were elucidated through an examination of the Gene Ontology (GO) Encyclopedia, the Kyoto Encyclopedia of Genes and Genomes (KEGG), and an enrichment analysis (GSEA). The GeneMANIA was used to validate the functions of nuak1-related genes.

RESULTS

Our analysis demonstrated that NUAK1 expression in tumour tissues exhibited a notable disparity from that observed in normal tissues, with elevated levels detected in STAD tissues. We used the GeneMANIA database to identify functionally similar genes with significantly higher expression for some genes in the unpaired group samples. An elevated NUAK1 expression level was found to correlate with a poorer overall survival (OS), disease-specific survival (DSS), and progression-free intervals (PFI). Additionally, immune infiltration analysis indicated a significant positive correlation between NUAK1 expression and various tumor-infiltrating immune cells, while a negative correlation was observed with T helper cell 17(Th17) cells. Furthermore, enrichment analysis was conducted to identify relevant biological features and pathways.

CONCLUSION

The expression levels of NUAK1 are significantly increased in STAD, and this heightened expression correlates with diminished OS, DSS, and PFI among affected patients. These observations indicate that NUAK1 has the potential to function as a prognostic biomarker for STAD and may represent a viable therapeutic target for intervention in its management.

摘要

背景

胃腺癌(STAD)是一项重大的全球健康负担,在癌症相关死亡率中占相当大的比例,而蛋白激酶NUAK1在细胞代谢、细胞周期调控、迁移和肿瘤进展中起着关键作用。然而,其与STAD预后及免疫浸润的关系尚未得到充分研究。

方法

利用来自癌症基因组图谱(TCGA)和基因型组织表达项目(GTEx)数据库的RNA测序数据,评估STAD肿瘤组织与正常组织中NUAK1表达的差异。此外,我们研究了NUAK1表达与患者预后以及免疫细胞浸润水平之间的相关性。通过检查基因本体论(GO)百科全书、京都基因与基因组百科全书(KEGG)以及富集分析(GSEA)来阐明潜在功能。使用GeneMANIA来验证nuak1相关基因的功能。

结果

我们的分析表明,肿瘤组织中的NUAK1表达与正常组织相比存在显著差异,STAD组织中检测到的水平升高。我们使用GeneMANIA数据库在未配对组样本中识别出一些表达明显更高的功能相似基因。发现NUAK1表达水平升高与较差的总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFI)相关。此外,免疫浸润分析表明NUAK1表达与各种肿瘤浸润免疫细胞之间存在显著正相关,而与辅助性T细胞17(Th17)细胞呈负相关。此外,进行了富集分析以识别相关的生物学特征和途径。

结论

STAD中NUAK1的表达水平显著升高,这种升高的表达与受影响患者的OS、DSS和PFI降低相关。这些观察结果表明,NUAK1有潜力作为STAD的预后生物标志物,并且可能是其治疗干预的一个可行靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9056/11655760/b35d3c4d629d/12672_2024_1688_Fig1_HTML.jpg

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