Biochimica et biophysica acta. Molecular basis of disease · 2026
Intratumoral Pseudomonas fragi inversely correlates with Jab1/COPS5 expression and improves prognosis in breast cancer.
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Zhang Qian, Wang Dujuan, Qin Kexin, Fan Wei, Wan Yuhang, Zhuo Guangzheng, Ji Lili, Liu Guohong, Pan Yunbao
Аннотация
OBJECTIVE: This study aimed to characterize the differential composition of intratumoral microbiota in breast cancer tissues with varying Jab1/COPS5 expression, evaluate their impact on tumor prognosis, progression, and immune cell infiltration.
METHODS: Jab1 expression was quantified via immunohistochemistry. Differential analysis of 2bRAD-M sequencing data was performed to screen and identify target bacterial species. Kaplan-Meier survival analysis was applied to evaluate the prognostic value of bacterial abundance. Integrative analysis of 2bRAD-M microbiome data and Digital Spatial Profiler (DSP) transcriptomic data was further conducted to dissect microbial regulation of immune cell infiltration. In vitro experiments validated the effects of target bacteria on tumor cell proliferation and neutrophil chemotaxis. In vivo, a Balb/c mouse breast cancer model was established via subcutaneous injection of 4T1 cells pre-treated with Pseudomonas fragi (P. fragi) to investigate bacterial effects on tumor growth and intratumoral neutrophil infiltration.
RESULTS: P. fragi and Ralstonia pickettii emerged as key taxa, with P. fragi abundance significantly associated with improved patient prognosis. In vitro, co-culture with P. fragi markedly reduced the proliferation and migration of breast cancer cells while attenuating neutrophil chemotaxis. In vivo, P. fragi pretreatment significantly inhibited tumor growth and decreased neutrophil infiltration in the tumor microenvironment, consistent with in vitro findings.
CONCLUSION: P. fragi within breast cancer tissues is inversely correlated with Jab1 expression, inhibiting tumor cell proliferation and suppressing neutrophil chemotaxis, and reducing tumor progression.
METHODS: Jab1 expression was quantified via immunohistochemistry. Differential analysis of 2bRAD-M sequencing data was performed to screen and identify target bacterial species. Kaplan-Meier survival analysis was applied to evaluate the prognostic value of bacterial abundance. Integrative analysis of 2bRAD-M microbiome data and Digital Spatial Profiler (DSP) transcriptomic data was further conducted to dissect microbial regulation of immune cell infiltration. In vitro experiments validated the effects of target bacteria on tumor cell proliferation and neutrophil chemotaxis. In vivo, a Balb/c mouse breast cancer model was established via subcutaneous injection of 4T1 cells pre-treated with Pseudomonas fragi (P. fragi) to investigate bacterial effects on tumor growth and intratumoral neutrophil infiltration.
RESULTS: P. fragi and Ralstonia pickettii emerged as key taxa, with P. fragi abundance significantly associated with improved patient prognosis. In vitro, co-culture with P. fragi markedly reduced the proliferation and migration of breast cancer cells while attenuating neutrophil chemotaxis. In vivo, P. fragi pretreatment significantly inhibited tumor growth and decreased neutrophil infiltration in the tumor microenvironment, consistent with in vitro findings.
CONCLUSION: P. fragi within breast cancer tissues is inversely correlated with Jab1 expression, inhibiting tumor cell proliferation and suppressing neutrophil chemotaxis, and reducing tumor progression.