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A model of coagulation-related genes for prediction of prognosis in lung adenocarcinoma and verification in vitro.
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Abstract
ObjectiveGiven the close link between abnormal coagulation function and lung adenocarcinoma (LUAD) progression, this study aims to identify coagulation-related biomarkers that influence LUAD prognosis and to validate the biological functions of key genes through in vitro experiments.MethodsWe obtained coagulation-related genes (CRGs) from the TCGA-LUAD and Genecards databases. To identify key CRGs, Cox and lasso analyses were conducted, leading to the establishment of a predictive model for the coagulation risk score (CRRS). The model's predictive accuracy was examined using Kaplan-Meier and receiver operating characteristic (ROC) curve, followed by external validation to ensure robustness. A nomogram was then created by integrating risk scores with clinical factors, enabling the quantification of survival probabilities for individual patients. Additional analyses examined the relationships between risk scores and functional pathways, tumor immune features, and chemotherapy drug sensitivity. Immunohistochemistry (IHC) was performed to validate ASPH expression. Finally, ASPH expression was silenced in A549 and NCI-H1975 cell lines, and the impact on tumor cell behavior was evaluated.ResultsThe model constructed in this article can effectively predict the prognosis of LUAD patients. CRRS is an independent prognostic factor for LUAD, and CRRS was significantly correlated with multiple clinical indicators. Additionally, immune checkpoint expression was meaningfully higher in high-risk patients compared to low-risk patients. IHC analysis revealed an increase in ASPH expression in LUAD specimens. Downregulation of ASPH impairs the malignant biological behavior of LUAD cells.ConclusionThe CRRS model provides reliable prognostic value for LUAD patients. ASPH could function as both a molecular marker and a potential treatment target for patients.
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