感染与肺癌进展和脑转移中的基质金属蛋白酶-9相关。

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

作者信息

Gao Lu, Jiang Feng

机构信息

Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.

BIOTARGET DX LLC, 7193 Somerton Ct, Hanover, Maryland 21076, USA.

出版信息

medRxiv. 2025 Apr 16:2025.04.15.25325903. doi: 10.1101/2025.04.15.25325903.

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.

摘要

基质金属蛋白酶(MMPs)是细胞外基质重塑的关键介质,在肺癌的进展和转移中起关键作用。新出现的证据表明,细菌病原体,如肺炎链球菌(SP),可调节MMP活性并促进肿瘤进展。本研究量化了肺癌组织中SP的丰度,并研究了其与MMP-9和MMP-2表达的关系,以及其对临床结局的影响。使用液滴数字PCR评估SP DNA水平,并通过免疫组织化学评估120例肺癌样本中MMP-9和MMP-2蛋白表达。SP丰度升高与MMP-9表达增加、肺癌晚期、脑转移负担加重和总生存期缩短显著相关(P < 0.05)。然而,SP丰度与MMP-2表达无相关性。这些发现突出了SP感染与肺癌进展之间通过MMP-9介导的细胞外基质降解和转移扩散的直接联系。靶向SP-MMP-9轴可能代表一种减轻转移和改善肺癌患者结局的新治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6e8a/12047908/a7d309baf332/nihpp-2025.04.15.25325903v1-f0001.jpg

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