Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses
IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.Met...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-01-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1029884/full |
| _version_ | 1797952055173709824 |
|---|---|
| author | Wenjie Li Rong Wang Wei Wang |
| author_facet | Wenjie Li Rong Wang Wei Wang |
| author_sort | Wenjie Li |
| collection | DOAJ |
| description | IntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p < 0.05).ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients. |
| first_indexed | 2024-04-10T22:40:21Z |
| format | Article |
| id | doaj.art-3893c3f106c64924b92877dc0e99d0f4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T22:40:21Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3893c3f106c64924b92877dc0e99d0f42023-01-16T05:22:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-01-011310.3389/fimmu.2022.10298841029884Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analysesWenjie LiRong WangWei WangIntroductionThere has been a cumulative interest in relationships between systemic lupus erythematosus (SLE) and cancer risk. Breast cancer is the most common cancer among women worldwide. However, the casual association and pathogenesis between SLE and breast cancer remains incompletely unknown.MethodsMendelian randomization (MR) analysis was first conducted to investigate the potential causality between SLE and breast cancer. Sensitivity analyses were applied to validate the reliability of MR results. Transcriptomic data analyses based on the Cancer Genome Atlas and Gene Expression Omnibus databases were then performed to identify and construct a SLE-related gene signature (SLEscore).ResultsThe MR analysis demonstrated that genetic predisposition to SLE was casually associated with the decreased risk of breast cancer in the East Asian cohort (odds ratios: 0.95, 95% confidence interval: 0.92-0.98, p=0.006). However, no casual associations were observed in the European population. Furthermore, sensitivity analyses proved the robustness of the present MR results. A prognostic SLEscore consisting of five SLE-related genes (RACGAP1, HMMR, TTK, TOP2A, and KIF15) could distribute patients with breast cancer into the high- and low-risk groups according to survival rates with good predictive ability (p < 0.05).ConclusionOur MR study provided evidence that genetic changes in SLE were significantly associated with the decreased risk of breast cancer in the East Asian population, while no causality was found in the European cohorts. Transcriptome data analyses indicated that the SLEscore could serve as a novel biomarker for predicting prognosis when breast cancer and SLE coexisted in patients.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1029884/fullsystemic lupus erythematosusbreast cancerMendelian randomizationtranscriptomic dataprevention |
| spellingShingle | Wenjie Li Rong Wang Wei Wang Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses Frontiers in Immunology systemic lupus erythematosus breast cancer Mendelian randomization transcriptomic data prevention |
| title | Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses |
| title_full | Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses |
| title_fullStr | Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses |
| title_full_unstemmed | Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses |
| title_short | Exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on Mendelian randomization and transcriptome data analyses |
| title_sort | exploring the causality and pathogenesis of systemic lupus erythematosus in breast cancer based on mendelian randomization and transcriptome data analyses |
| topic | systemic lupus erythematosus breast cancer Mendelian randomization transcriptomic data prevention |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1029884/full |
| work_keys_str_mv | AT wenjieli exploringthecausalityandpathogenesisofsystemiclupuserythematosusinbreastcancerbasedonmendelianrandomizationandtranscriptomedataanalyses AT rongwang exploringthecausalityandpathogenesisofsystemiclupuserythematosusinbreastcancerbasedonmendelianrandomizationandtranscriptomedataanalyses AT weiwang exploringthecausalityandpathogenesisofsystemiclupuserythematosusinbreastcancerbasedonmendelianrandomizationandtranscriptomedataanalyses |