Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer
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...
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| Format: | Article |
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Springer
2025-04-01
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| Series: | Discover Oncology |
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| Online Access: | https://doi.org/10.1007/s12672-025-02237-4 |
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| author | Ronglin Li Zhenniu Lei Zhaoke Wen Yifan Zhou Yunzhi Ma Junqi Qin Xiaoyan Huang Shuping Huang Shucong Peng Shengjing Liang Yonglong Zhong |
| author_facet | Ronglin Li Zhenniu Lei Zhaoke Wen Yifan Zhou Yunzhi Ma Junqi Qin Xiaoyan Huang Shuping Huang Shucong Peng Shengjing Liang Yonglong Zhong |
| author_sort | Ronglin Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b1d60672f4374060aef88efb4deb188d |
| institution | OA Journals |
| issn | 2730-6011 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Springer |
| record_format | Article |
| series | Discover Oncology |
| spelling | doaj-art-b1d60672f4374060aef88efb4deb188d2025-08-20T02:30:26ZengSpringerDiscover Oncology2730-60112025-04-0116111210.1007/s12672-025-02237-4Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancerRonglin Li0Zhenniu Lei1Zhaoke Wen2Yifan Zhou3Yunzhi Ma4Junqi Qin5Xiaoyan Huang6Shuping Huang7Shucong Peng8Shengjing Liang9Yonglong Zhong10Department of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesDepartment of Thoracic Surgery, the People’S Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical SciencesAbstract 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.https://doi.org/10.1007/s12672-025-02237-4Fasting blood glucosePlasma proteinsLung cancerLung cancer subtypesMendelian randomization |
| spellingShingle | Ronglin Li Zhenniu Lei Zhaoke Wen Yifan Zhou Yunzhi Ma Junqi Qin Xiaoyan Huang Shuping Huang Shucong Peng Shengjing Liang Yonglong Zhong Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer Discover Oncology Fasting blood glucose Plasma proteins Lung cancer Lung cancer subtypes Mendelian randomization |
| title | Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer |
| title_full | Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer |
| title_fullStr | Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer |
| title_full_unstemmed | Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer |
| title_short | Mendelian randomization study on the causal relationships among fasting blood glucose, plasma proteins, and squamous cell lung cancer |
| title_sort | mendelian randomization study on the causal relationships among fasting blood glucose plasma proteins and squamous cell lung cancer |
| topic | Fasting blood glucose Plasma proteins Lung cancer Lung cancer subtypes Mendelian randomization |
| url | https://doi.org/10.1007/s12672-025-02237-4 |
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