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铜死亡相关基因 DLAT 是胃癌预后和免疫微环境的标志物,影响细胞的侵袭和迁移。

Cuproptosis-related gene DLAT is a biomarker of the prognosis and immune microenvironment of gastric cancer and affects the invasion and migration of cells.

机构信息

Department of Histology and Embryology, Shenyang Medical College, Shenyang, Liaoning, China.

Shenyang Medical College, Shenyang, Liaoning, China.

出版信息

Cancer Med. 2024 Jul;13(14):e70012. doi: 10.1002/cam4.70012.

DOI:10.1002/cam4.70012
PMID:39031012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11258438/
Abstract

OBJECTIVE

Cuproptosis is a novel cell death dependent on mitochondrial respiration and regulated by copper. This study aimed to investigate the cuproptosis-related gene DLAT potential value in gastric cancer (GC).

METHODS

Bioinformatics was used to analyze DLAT expression. DLAT expression in GC cell lines was detected using qRT-PCR. Cell proliferation ability was assessed using CCK8 and cell cycle assay. Cell migration and invasion were assessed using wound healing and transwell assay. A prognostic assessment was performed through survival and Cox regression analysis. DLAT protein expression was analyzed through HPA immunohistochemistry. Biological functions and processes were analyzed through GO and KEGG enrichment analysis and PPI. Correlation with immune cell infiltration and immune checkpoint genes was analyzed for DLAT.

RESULTS

DLAT expression was upregulated in GC tissues and cells and correlated with shorter survival for patients. Age, gender, histological typing, lymph node metastasis, and distant metastasis were identified as independent prognostic factors affecting OS in GC. DLAT protein was upregulated in GC. The biological functions and pathways enriched in DLAT were mainly linked to mitochondrial respiration and the TCA cycle. The expression of DLAT was found to be positively correlated with the infiltration of Th and Th2 immune cells and only positively correlated with the expression of the BTN2A1 immune checkpoint gene.

CONCLUSION

DLAT has the potential to serve as a prognostic assessment factor in GC. The expression of DLAT was correlated with immune infiltration and tumor immune escape, providing a new target for immunotherapy of GC.

摘要

目的

铜死亡依赖于线粒体呼吸,受铜调节,是一种新的细胞死亡方式。本研究旨在探讨胃腺癌(GC)中与铜死亡相关的基因 DLAT 的潜在价值。

方法

使用生物信息学分析 DLAT 表达。使用 qRT-PCR 检测 GC 细胞系中 DLAT 的表达。通过 CCK8 和细胞周期检测评估细胞增殖能力。通过划痕愈合和 Transwell 检测评估细胞迁移和侵袭。通过生存和 Cox 回归分析进行预后评估。通过 HPA 免疫组化分析 DLAT 蛋白表达。通过 GO 和 KEGG 富集分析和 PPI 分析分析生物学功能和过程。分析 DLAT 与免疫细胞浸润和免疫检查点基因的相关性。

结果

DLAT 在 GC 组织和细胞中表达上调,与患者的生存时间缩短相关。年龄、性别、组织学分型、淋巴结转移和远处转移被确定为影响 GC 患者 OS 的独立预后因素。GC 中 DLAT 蛋白表达上调。在 DLAT 中富集的生物学功能和途径主要与线粒体呼吸和 TCA 循环有关。发现 DLAT 的表达与 Th 和 Th2 免疫细胞的浸润呈正相关,仅与免疫检查点基因 BTN2A1 的表达呈正相关。

结论

DLAT 有望成为 GC 的预后评估因素。DLAT 的表达与免疫浸润和肿瘤免疫逃逸相关,为 GC 的免疫治疗提供了新的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/2c3a960264e4/CAM4-13-e70012-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/ee386629997a/CAM4-13-e70012-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/4195695b9e82/CAM4-13-e70012-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/36a635ad33c7/CAM4-13-e70012-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/4ea8ccdd779b/CAM4-13-e70012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/778909d2bc61/CAM4-13-e70012-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/2c3a960264e4/CAM4-13-e70012-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/ee386629997a/CAM4-13-e70012-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/4195695b9e82/CAM4-13-e70012-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/36a635ad33c7/CAM4-13-e70012-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/4ea8ccdd779b/CAM4-13-e70012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/778909d2bc61/CAM4-13-e70012-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da58/11258438/2c3a960264e4/CAM4-13-e70012-g003.jpg

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