肺扁平上皮癌における全身性止血に関連する新規ceRNAネットワークの同定とその予後への影響

Lung cancer is one of the most common malignancies, characterized by a wide prognosis spectrum, different histological subtypes, and a high mortality rate. Hemostatic system imbalance in patients with lung cancer often leads to increased mortality. Intracellular RNAs that share common miRNA binding sites create a competing endogenous RNA (ceRNA) network that plays an important role in gene expression regulation. The emerging role of ceRNAs in tumor development is increasingly being recognized; however, their connection to hemostatic system imbalance in lung squamous cell carcinoma (LUSC) remains unclear. In this study, RNA-seq data of LUSC and normal tissues were downloaded from the TCGA data portal. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and lncRNAs (DElncRNAs) between LUSC and corresponding paracancerous tissues were analyzed using the DESeq2 package in R statistical software. Hemostasis-related genes linked to coagulation and complement cascades (hsa04610) and platelet activation (hsa04611) pathways were identified using the KEGGREST package. The ceRNA network associated with system hemostasis was constructed using differentially expressed RNAs (DERNAs), including mRNAs, lncRNAs, and miRNAs. The GO and KEGG enrichment analysis of DEmRNAs was conducted using the enrichR package. Hazard ratio (HR) and Kaplan-Meier curve were employed to assess the prognostic value of DERNAs using the survival and survminer packages. A ceRNA network comprising 100 hemostasis-related genes, 5 miRNAs, and 57 lncRNAs was constructed. Of these, 19 hemostasis genes, one miRNA (miR-23-3p), and 6 lncRNAs (LINC01615, LINC00707, LINC00702, FEZF1-AS1, DLX6-AS1, CLRN1-AS1) were significantly associated with prognosis in LUSC. Based on correlation analysis, MEF2C-AS1/miR-429/F8, RAP1A, GNAI2, C3AR1, F13A1, P2RY12, LCP2, C1QC axis and CASC11, CASC9, PVT1, BBOX1-AS1/ miR-23b-3p/ PLAU axis may represent key pathways involved in hemostatic system imbalance and the pathogenesis of LUSC. Our analysis revealed a complex ceRNA network associated with system hemostasis and the prognosis of LUSC. These findings may contribute to the development of personalized therapies and valuable prognostic biomarkers for LUSC patients.