Streptococcus pneumoniae infection is associated with matrix metalloproteinase-9 in lung cancer progression and brain metastases

Tumor progression and metastasis, particularly brain metastases, are major causes of mortality in lung cancer. Emerging evidence indicates that microbial infections can influence tumor biology. We previously identified Streptococcus pneumoniae (SP) as a contributing factor to lung cancer progression. Matrix metalloproteinases (MMPs) are key enzymes involved in extracellular matrix remodeling and have been implicated in promoting metastatic dissemination. This study investigated the association between SP infection, MMP expression, and clinical outcomes in 126 lung cancer tissues. SP DNA levels were quantified using droplet digital PCR, and MMP protein expression was assessed by immunohistochemistry. Elevated SP abundance was significantly correlated with increased MMP-9 expression, advanced tumor stage, presence of brain metastases, and reduced overall survival (P < 0.05), whereas no significant association was observed with MMP-2. Therefore, SP infection is associated with lung cancer progression and metastasis through its correlation with MMP-9-mediated extracellular matrix remodeling. This association highlights a potential therapeutic target for limiting metastatic spread and improving patient outcomes; however, functional studies are required to confirm its mechanistic role in lung tumorigenesis.