空腹血糖、血浆蛋白与肺鳞状细胞癌因果关系的孟德尔随机化研究

Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer.

作者信息

Li Ronglin, Lei Zhenniu, Wen Zhaoke, Zhou Yifan, Ma Yunzhi, Qin Junqi, Huang Xiaoyan, Huang Shuping, Peng Shucong, Liang Shengjing, Zhong Yonglong

机构信息

Department of Thoracic Surgery, the People'S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, 6 Taoyuan Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China.

出版信息

Discov Oncol. 2025 Apr 22;16(1):588. doi: 10.1007/s12672-025-02237-4.

DOI:10.1007/s12672-025-02237-4

PMID:40263141

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12014989/

Abstract

BACKGROUND

Squamous cell lung cancer (SQCLC) represents the second most common subtype of lung cancer (LC) with characteristics of treatment resistance. Plasma proteins often influence levels of fasting blood glucose (FBG), consequently impacting LC. However, the precise role of FBG in this association remains unclear.

OBJECTIVE

To investigate the causal relationships of FBG with LC and its subtypes, plasma proteins, and SQCLC, as well as the mediating role of FBG.

METHODS

Mendelian randomization (MR) analysis was employed to assess the causal associations of FBG with LC and its subtypes, plasma proteins and SQCLC, and plasma proteins and FBG, using the two-step MR approach with the primary method being Inverse Variance Weighted (IVW). Protein-Protein Interaction (PPI) network was utilized to identify hub genes of plasma proteins causally linked to SQCLC.

RESULTS

FBG was a risk factor for SQCLC (OR: 1.376, 95% CI 1.017-1.862, P = 0.038) but had no significant causal associations with LC and other subtypes (P > 0.05). Furthermore, 54 plasma proteins had significant causal associations with SQCLC (P < 0.05). EEF2 K (OR: 1.111, 95% CI 1.015-1.216, P = 0.023) and SSR1 (OR: 0.546, 95% CI 0.487-0.613, P < 0.001) were identified as a risk and protective factor for FBG, respectively. Mediation analysis indicated a significant negative mediating effect of FBG in the causal relationship between SSR1 and SQCLC (B = - 0.193, 95% CI - 0.312-0.074, P = 0.001), with a mediation proportion of 44.4%.

CONCLUSION

Our study revealed FBG as a risk factor for SQCLC and demonstrated the mediating role of FBG in the causal association between SSR1 and SQCLC.

摘要

背景

肺鳞状细胞癌（SQCLC）是肺癌（LC）的第二大常见亚型，具有治疗抵抗的特征。血浆蛋白常影响空腹血糖（FBG）水平，进而影响肺癌。然而，FBG在这种关联中的具体作用仍不清楚。

目的

探讨FBG与肺癌及其亚型、血浆蛋白和SQCLC之间的因果关系，以及FBG的中介作用。

方法

采用孟德尔随机化（MR）分析，使用两步MR方法，主要方法为逆方差加权（IVW），评估FBG与肺癌及其亚型、血浆蛋白和SQCLC以及血浆蛋白和FBG之间的因果关联。利用蛋白质-蛋白质相互作用（PPI）网络识别与SQCLC有因果关系的血浆蛋白的枢纽基因。

结果

FBG是SQCLC的危险因素（OR：1.376，95%CI 1.017-1.862，P = 0.038），但与肺癌及其他亚型无显著因果关联（P > 0.05）。此外，54种血浆蛋白与SQCLC有显著因果关联（P < 0.05）。EEF2 K（OR：1.111，95%CI 1.015-1.216，P = 0.023）和SSR1（OR：0.546，95%CI 0.487-0.613，P < 0.001）分别被确定为FBG的危险因素和保护因素。中介分析表明，FBG在SSR1与SQCLC的因果关系中具有显著的负中介作用（B = - 0.193，95%CI - 0.312-0.074，P = 0.001），中介比例为44.4%。