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流行病学和转录组数据揭示了2型糖尿病和非小细胞肺癌中共同的基因特征及免疫细胞浸润。

Epidemiological and transcriptome data identify shared gene signatures and immune cell infiltration in type 2 diabetes and non-small cell lung cancer.

作者信息

Yuan Qian, Li Long, Wang Liu-Shun, Xing Shi-Gui

机构信息

Department of Thoracic surgery, Nan Jing Gaochun people's Hospital (The Gaochun Affiliated Hospital of Jiang Su University), 210000, Nanjing, Jiangsu, China.

出版信息

Diabetol Metab Syndr. 2024 Mar 12;16(1):64. doi: 10.1186/s13098-024-01278-z.

DOI:10.1186/s13098-024-01278-z
PMID:38468345
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10929160/
Abstract

BACKGROUND

Numerous previous studies have reported an association between type 2 diabetes mellitus (T2DM) and lung cancer risk, but the underlying mechanism of the interaction remains unclear. This study aimed to investigate the shared genetic features and immune infiltration processes between lung cancer and T2DM.

METHODS

Epidemiological data from the National Health and Nutrition Examination Survey (NHANES) 2000-2018 was used to explore the relationship between lung cancer and diabetes systematically. In addition, we also used bioinformatics methods to analyze the transcriptome data from the Gene Expression Omnibus (GEO) to explore the potential functional mechanisms from the perspective of genes and immune infiltration.

RESULTS

Logistic regression analysis showed that prediabetes (OR = 3.289,95%CI 1.231, 8.788, p = 0.01760, model 3)and type 2 diabetes (OR = 3.032 95%CI,1.015, 9.054, p = 0.04689) were significantly associated with an increased risk of lung cancer after adjusting for multiple covariates. Data from NHANES showed an inverted U-shaped relationship between fasting blood glucose and glycosylated haemoglobin and the risk of lung cancer (P for non-linear < 0.001). Transcriptome data showed that we screened 57 co-DEGs, of which 25 were up-regulated co-DEGs and 32 were down-regulated. Ten core DEGs were identified by bioinformatics analysis, which were SMC6, CDC27, CDC7, RACGAP1, SMC4, NCF4, NCF1, NCF2, SELPLG and CFP. Correlation analysis showed that some core DEGs were significantly associated with simultaneous dysregulation of immune cells.

CONCLUSION

The identified core genes of NSCLC and T2DM are associated with dysregulated immune cells, which provides a potential research avenue for diagnosing and treating lung cancer combined with diabetes.

摘要

背景

此前众多研究报告了2型糖尿病（T2DM）与肺癌风险之间的关联，但二者相互作用的潜在机制仍不清楚。本研究旨在探究肺癌与T2DM之间共同的遗传特征和免疫浸润过程。

方法

利用2000 - 2018年美国国家健康与营养检查调查（NHANES）的流行病学数据，系统地探究肺癌与糖尿病之间的关系。此外，我们还使用生物信息学方法分析来自基因表达综合数据库（GEO）的转录组数据，从基因和免疫浸润的角度探究潜在的功能机制。

结果

逻辑回归分析显示，在调整多个协变量后，糖尿病前期（OR = 3.289，95%CI 1.231，8.788，p = 0.01760，模型3）和2型糖尿病（OR = 3.032，95%CI 1.015，9.054，p = 0.04689）与肺癌风险增加显著相关。NHANES的数据显示空腹血糖和糖化血红蛋白与肺癌风险之间呈倒U型关系（非线性P < 0.001）。转录组数据显示，我们筛选出57个共同差异表达基因（co-DEGs），其中25个是上调的co-DEGs，32个是下调的。通过生物信息学分析确定了10个核心差异表达基因，分别为SMC6、CDC27、CDC7、RACGAP1、SMC4、NCF4、NCF1、NCF2、SELPLG和CFP。相关性分析表明一些核心差异表达基因与免疫细胞的同时失调显著相关。

结论

所确定的非小细胞肺癌（NSCLC）和T2DM的核心基因与免疫细胞失调有关，这为结合糖尿病诊断和治疗肺癌提供了一条潜在的研究途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a433/10929160/7896fee91b16/13098_2024_1278_Fig12_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a433/10929160/3e80d5a6056d/13098_2024_1278_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a433/10929160/1030094d5df3/13098_2024_1278_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a433/10929160/7c6bd4174788/13098_2024_1278_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a433/10929160/810433fc5883/13098_2024_1278_Fig10_HTML.jpg
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