Neutrophil extracellular traps-related long non-coding RNAs have emerged as significant prognostic indicators for gastric cancer, offering new avenues for personalized treatment strategies. Recent research published on March 6, 2025, highlights the development of a prognostic signature, termed NlncSig, composed of four related lncRNAs. This study draws on extensive data from the Cancer Genome Atlas (TCGA), aiming to improve the predictive capabilities for patient outcomes and responses to immunotherapy.
Gastric cancer (GC) remains a pressing global health issue, with over one million new cases diagnosed annually. Its advanced stages often limit effective treatment options, leading to poor patient prognosis. Current therapies including surgery, chemotherapy, and immunotherapy fail to consistently improve survival rates, especially among advanced or metastatic cases. Researchers now face the challenge of identifying reliable biomarkers to tailor targeted therapies for GC, as standard diagnostic markers have proven insufficient.
Within the complex cancer biology, neutrophil extracellular traps (NETs) represent both immune defense mechanisms and potential contributors to tumor progression. Prior studies have revealed NETs' associations with cancer metastasis and treatment resistance, prompting investigations of their long non-coding RNA (lncRNA) counterparts. The latest study identifies significant roles for NETs-related lncRNAs by constructing the NlncSig, which correlates with clinical outcomes for GC patients.
The researchers identified 78 lncRNAs linked with NETs' enrichment scores through Pearson correlation, enriched by using statistical methods including univariate and multivariate Cox regression analyses. They found four key NETs-related lncRNAs—LINC01150, LINC02773, AL049775.1, and AC026329.1—that demonstrate strong prognostic capabilities. The formulated risk score from these lncRNAs allows physicians to categorize patients based on their likelihood of poor outcomes. This classification provides invaluable insights, especially concerning immunotherapy response.
Notably, patients classified within the high-risk group, indicated by elevated risk scores, showed significantly poorer outcomes and lower rates of effective immunotherapy responses. Conversely, those with lower risk scores exhibited more favorable outcomes, underscoring the potential of the NlncSig as a treatment guide. One of the standout findings emanates from LINC01150, found to promote proliferation, migration, and invasion of GC cells. This oncogenic lncRNA showcases how NETs can influence tumor behavior and treatment responses.
The clinical relevance of the NlncSig appears promising, supported by the validation offered through comprehensive statistical evaluations. The multivariate regression analyses confirm the risk score as an independent prognostic factor, showcasing strong predictive accuracy across various cohorts. Using this risk assessment, clinicians can more adeptly strategize treatment plans, potentially enhancing patient outcomes.
Additional investigations revealed fascinating links between NlncSig and the tumor microenvironment's immune composition. Higher proportions of immunosuppressive cells, such as M2 macrophages, were noted among high-risk patients, contrasted with the presence of activated T cells among low-risk patients. This stark difference suggests NlncSig's association with immune evasion mechanisms, elucidated through the TIDE scoring system, emphasizing the need for enhanced immunotherapy strategies.
Future research directions will focus on analysing LINC01150's mechanistic roles, promoting greater clarity around how these lncRNAs modulate tumor and immune dynamics. The study sets the foundation for large-scale validations and potential therapeutic applications centered on NETs-related markers.
Overall, this research not only advances our comprehension of gastric cancer's complex biology but also suggests integrative approaches to improve prognostic capabilities and treatment responsiveness. The exploration of NETs-related lncRNAs heralds new possibilities for personalizing therapy and enhancing care for gastric cancer patients.