Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma
ABSTRACT Objective Several observational studies have identified an association between plasma proteins and hepatocellular carcinoma (HCC). This study aimed to explore the potential causal relationship between the circulating protein‐to‐protein ratio and the morbidity risk of HCC. Methods Genetic as...
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2025-01-01
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| Online Access: | https://doi.org/10.1002/cam4.70570 |
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| author | Qiuyuan Yue Xiaoxia Li Xiaoye Wan Xi Lin Yueming Li Mingwei Zhang Shaohua Xu |
| author_facet | Qiuyuan Yue Xiaoxia Li Xiaoye Wan Xi Lin Yueming Li Mingwei Zhang Shaohua Xu |
| author_sort | Qiuyuan Yue |
| collection | DOAJ |
| description | ABSTRACT Objective Several observational studies have identified an association between plasma proteins and hepatocellular carcinoma (HCC). This study aimed to explore the potential causal relationship between the circulating protein‐to‐protein ratio and the morbidity risk of HCC. Methods Genetic association data for circulating plasma proteins and 2821 protein‐to‐protein ratios were sourced from the UKB PPP and Suhre's study. Genetic association data for HCC were sourced from the FinnGen cohort (finngen‐R11‐HCC) and the IEU OpenGWAS project (ieu‐b‐4953). Subsequently, a two‐sample Mendelian randomization (MR) and drug‐targeted MR approach were used to evaluate causality associations. To bolster the robustness of our findings, we conducted a series of sensitivity analyses. Results Eight protein–protein pairs were identified as causal factors for HCC in the two independent cohorts. For each standard deviation increase in protein–protein pair expression, susceptibility to HCC fluctuated from 0.4974 (95% confidence interval [CI]: 0.2506–0.9871) for the LAT2/SPRY2 protein pair to 1.9763 (95% CI: 1.3009–3.0026) for the ERBIN/LAT2 protein pair. However, among the significant protein pairs, only one circulating protein, TDRKH (odds ratio: 0.5964, 95% CI: 0.4196–0.8476), was causally associated with HCC. Conclusion Using multiple datasets and methods, eight protein–protein pairs were identified as having causal associations with HCC. Protein–protein interactions can provide meaningful findings beyond simple pQTL analysis. |
| format | Article |
| id | doaj-art-7b2bb597fa1446d598bade9201f2b21f |
| institution | Kabale University |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
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| series | Cancer Medicine |
| spelling | doaj-art-7b2bb597fa1446d598bade9201f2b21f2025-01-13T13:22:39ZengWileyCancer Medicine2045-76342025-01-01141n/an/a10.1002/cam4.70570Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular CarcinomaQiuyuan Yue0Xiaoxia Li1Xiaoye Wan2Xi Lin3Yueming Li4Mingwei Zhang5Shaohua Xu6Department of Radiology, Clinical Oncology School of Fujian Medical University Fujian Cancer Hospital Fuzhou Fujian ChinaDepartment of Radiotherapy, Cancer Center The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian ChinaDepartment of Blood Transfusion FuZhou Second General Hospital Fuzhou Fujian ChinaDepartment of Radiology, Clinical Oncology School of Fujian Medical University Fujian Cancer Hospital Fuzhou Fujian ChinaDepartment of Radiology The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian ChinaDepartment of Radiotherapy, Cancer Center The First Affiliated Hospital of Fujian Medical University Fuzhou Fujian ChinaDepartment of Hepatobiliary and Pancreatic Surgery, Clinical Oncology School of Fujian Medical University Fujian Cancer Hospital Fuzhou Fujian ChinaABSTRACT Objective Several observational studies have identified an association between plasma proteins and hepatocellular carcinoma (HCC). This study aimed to explore the potential causal relationship between the circulating protein‐to‐protein ratio and the morbidity risk of HCC. Methods Genetic association data for circulating plasma proteins and 2821 protein‐to‐protein ratios were sourced from the UKB PPP and Suhre's study. Genetic association data for HCC were sourced from the FinnGen cohort (finngen‐R11‐HCC) and the IEU OpenGWAS project (ieu‐b‐4953). Subsequently, a two‐sample Mendelian randomization (MR) and drug‐targeted MR approach were used to evaluate causality associations. To bolster the robustness of our findings, we conducted a series of sensitivity analyses. Results Eight protein–protein pairs were identified as causal factors for HCC in the two independent cohorts. For each standard deviation increase in protein–protein pair expression, susceptibility to HCC fluctuated from 0.4974 (95% confidence interval [CI]: 0.2506–0.9871) for the LAT2/SPRY2 protein pair to 1.9763 (95% CI: 1.3009–3.0026) for the ERBIN/LAT2 protein pair. However, among the significant protein pairs, only one circulating protein, TDRKH (odds ratio: 0.5964, 95% CI: 0.4196–0.8476), was causally associated with HCC. Conclusion Using multiple datasets and methods, eight protein–protein pairs were identified as having causal associations with HCC. Protein–protein interactions can provide meaningful findings beyond simple pQTL analysis.https://doi.org/10.1002/cam4.70570circulating proteinshepatocellular carcinomaMendelian randomizationprotein‐to‐protein ratio |
| spellingShingle | Qiuyuan Yue Xiaoxia Li Xiaoye Wan Xi Lin Yueming Li Mingwei Zhang Shaohua Xu Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma Cancer Medicine circulating proteins hepatocellular carcinoma Mendelian randomization protein‐to‐protein ratio |
| title | Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma |
| title_full | Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma |
| title_fullStr | Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma |
| title_full_unstemmed | Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma |
| title_short | Assessing the Causal Effect of Circulating Protein‐To‐Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma |
| title_sort | assessing the causal effect of circulating protein to protein ratio on the risk of morbidity of hepatocellular carcinoma |
| topic | circulating proteins hepatocellular carcinoma Mendelian randomization protein‐to‐protein ratio |
| url | https://doi.org/10.1002/cam4.70570 |
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