International journal of women's health · 2026
Seipin as a Putative Protective Factor for Breast Cancer: Evidence from Mendelian Randomization Analysis.
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Zeng Junfeng, Wang Xinxu, Fan Luxuan, Bai Tao, Jia Hongyan, Yang Jing
Аннотация
OBJECTIVE: To investigate the causal association between Seipin and breast cancer risk using the Mendelian randomization (MR) approach.
METHODS: Genome-wide association study (GWAS) data for Seipin and breast cancer were analyzed, and genetic variants associated with Seipin were selected as instrumental variables (IVs). Inverse variance weighting (IVW) was used as the primary analytical method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode MR analyses to evaluate the causal relationship between Seipin and breast cancer risk. Furthermore, immunohistochemistry was performed to detect Seipin expression in pathological specimens from patients with breast cancer and those with mammary hyperplasia, and the correlation between Seipin expression and clinicopathological characteristics was analyzed.
RESULTS: MR analyses indicated that Seipin was inversely associated with breast cancer risk (IVW: OR = 0.89, 95% CI: 0.83-0.96, P < 0.05). Consistent with this, immunohistochemical results showed lower Seipin expression in breast cancer tissues than in mammary hyperplasia tissues, and its low expression was correlated with adverse clinicopathological features. Further independent validation using the TCGA-BRCA cohort recapitulated reduced BSCL2 expression in tumor versus adjacent normal tissues (P = 9.58 × 10-3).
CONCLUSION: MR combined with immunohistochemistry and independent public database validation suggests that Seipin may serve as a potential protective factor closely related to the occurrence and progression of breast cancer. Further functional studies are needed to elucidate the underlying mechanisms.
METHODS: Genome-wide association study (GWAS) data for Seipin and breast cancer were analyzed, and genetic variants associated with Seipin were selected as instrumental variables (IVs). Inverse variance weighting (IVW) was used as the primary analytical method, supplemented by MR-Egger, weighted median, simple mode, and weighted mode MR analyses to evaluate the causal relationship between Seipin and breast cancer risk. Furthermore, immunohistochemistry was performed to detect Seipin expression in pathological specimens from patients with breast cancer and those with mammary hyperplasia, and the correlation between Seipin expression and clinicopathological characteristics was analyzed.
RESULTS: MR analyses indicated that Seipin was inversely associated with breast cancer risk (IVW: OR = 0.89, 95% CI: 0.83-0.96, P < 0.05). Consistent with this, immunohistochemical results showed lower Seipin expression in breast cancer tissues than in mammary hyperplasia tissues, and its low expression was correlated with adverse clinicopathological features. Further independent validation using the TCGA-BRCA cohort recapitulated reduced BSCL2 expression in tumor versus adjacent normal tissues (P = 9.58 × 10-3).
CONCLUSION: MR combined with immunohistochemistry and independent public database validation suggests that Seipin may serve as a potential protective factor closely related to the occurrence and progression of breast cancer. Further functional studies are needed to elucidate the underlying mechanisms.