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Streptococcus pneumoniae infection is associated with Matrix Metalloproteinase-9 in Lung Cancer Progression and Brain Metastases

Gao, L.; jiang, F.

2025-04-16 oncology
10.1101/2025.04.15.25325903 medRxiv
Show abstract

Matrix metalloproteinases (MMPs) are critical mediators of extracellular matrix remodeling, playing a pivotal role in the progression and metastasis of lung cancer. Emerging evidence indicates that bacterial pathogens, such as Streptococcus pneumoniae (SP), can modulate MMP activity and contribute to tumor progression. This study quantified SP abundance in lung cancer tissues and investigated its relationship with MMP-9 and MMP-2 expression, as well as its impact on clinical outcomes. SP DNA levels were assessed using droplet digital PCR, and MMP-9 and MMP-2 protein expression were evaluated by immunohistochemistry in 120 lung cancer samples. Elevated SP abundance was significantly associated with increased MMP-9 expression, advanced lung cancer stages, greater brain metastases burden, and reduced overall survival (P < 0.05). However, SP abundance showed no correlation with MMP-2 expression. These findings highlight a direct link between SP infection and lung cancer progression through MMP-9-mediated extracellular matrix degradation and metastatic spread. Targeting the SP-MMP-9 axis may represent a novel therapeutic approach to mitigate metastasis and improve patient outcomes in lung cancer.

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