Despite advancements in lung squamous cell carcinoma (LUSC) diagnosis and treatment, patient outcomes remain unfavorable. The potential of microbiome-based prognostic biomarkers and therapeutic targets remains largely unexplored. This study delves into the complex interplay between the lung microbiome and genetic biomarkers, identifying specific microbial-based and mRNA associated with prognosis in LUSC.
LUSC, a major histological subtype of non-small cell lung cancer (NSCLC), accounts for a significant portion of lung cancer cases globally. Despite progress in diagnostic and treatment methods, LUSC patients face poor outcomes, with a five-year survival rate under 20% and a 33% chance of local recurrence within 2 years. This highlights the urgent need for novel prognostic biomarkers and therapeutic targets to improve patient outcomes.
Recent research has emphasized the critical impact of the tumor microenvironment, including microbial communities, on cancer initiation and progression. The human microbiome, particularly the gut microbiome, has been found to affect systemic inflammation, immune responses, and even the efficacy of cancer therapies. Microbial dysbiosis, an imbalance in microbial communities, has been implicated in various malignancies, including colorectal, gastric, and liver cancers.
These findings suggest that the microbiome may modulate tumor behavior through multiple mechanisms, including modulation of the immune system, production of microbial metabolites, and alteration of the tumor microenvironment. In the context of lung cancer, the lung microbiome is of particular interest. The lung, once considered a sterile environment, is now known to harbor a diverse microbial community. Variations in the lung microbiome have been connected to chronic respiratory conditions and might influence the pathogenesis of lung cancer.
Specific microbial taxa have been linked to inflammatory pathways that could contribute to tumor initiation and progression. For instance, specific bacteria can trigger chronic inflammation, a recognized risk factor for cancer. Moreover, microbial metabolites like short-chain fatty acids and secondary bile acids can affect cellular proliferation, apoptosis, and DNA repair mechanisms.
Despite the growing recognition of the microbiome's role in cancer, the specific impact of microbial communities within the lung on LUSC prognosis has not been thoroughly investigated. Given the intricate interplay between the microbiome and the host immune system, understanding the microbial composition associated with LUSC could provide valuable insights into the mechanisms driving cancer progression and identify potential biomarkers for prognosis and therapeutic targets.
This study aims to identify prognostic microbial markers in LUSC by comprehensively analyzing microbial genus-level abundance and RNA-Seq data. The researchers hypothesized that specific microbial genera are significantly associated with LUSC prognosis and that integrating these microbial markers with mRNA expression data can enhance the prognostic accuracy of existing models.