Abstract
Background: Cancer is considered one of the most lethal diseases worldwide. Venous thromboembolism (VTE) is the second leading cause of death in cancer patients. As one of the most reproducible predictors of thromboembolism, the D-dimer level is commonly considered by oncologists. Previous studies have demonstrated that the most correlated genes at the D-dimer level are F3, F5 and FGA. Methods: Using data from TCGA and multiple webtools, including GEPIA2, UALCAN, TIMER2.0, Kaplan-Meier Plotter and CIBERSORTx, we analyzed the tumor mutation burden (TMB), microsatellite instability (MSI) and functions of D-dimer-related genes in cancer. Validation was conducted via quantitative real-time polymerase chain reaction (qRT-PCR) and independent GEO + GTEx cohort. All statistical analyses were performed in R software and GraphPad Prism 9. Results: F3, F5 and FGA were expressed differently in multiple cancer types. TMB, MSI and anti-PD1/PDL1 therapy responses were correlated with D-dimer-related gene expression. D-Dimer-related genes expression affect the survival of cancer patients. F3 and F5 functioned in TGF-beta signaling. F3 and F5 were related to immunity and affected the fraction of CD8+ T cells by upregulating the TGF-beta signaling pathway, forming an F3, F5/TGF-beta signaling/CD8+ T cell axis. Conclusion: F3, F5 and FGA serve as satisfactory GC multibiomarkers and potentially influence the immune microenvironment and survival of cancer patients by influencing TGF-beta signaling.
Highlights
Cancer is considered a fatal disease worldwide
F3, F5 and fibrinogen alpha chain (FGA) serve as satisfactory gastric cancer (GC) multibiomarkers and potentially influence the immune microenvironment and survival of cancer patients by influencing TGF-beta signaling
To explore the value of the D-dimer-related genes F3, F5 and FGA, we conducted a pan-cancer study of these three genes and found a correlation among them and tumor mutation burden (TMB), microsatellite instability (MSI) and immune-related genes
Summary
Cancer is considered a fatal disease worldwide. In 2020, approximately 1,806,590 new cancer cases and 606,520 cancer deaths were expected in the United States (Siegel et al, 2020). Traditional cancer therapies rely on surgery, chemotherapy and radiotherapy. These treatment methods have not provided a satisfactory prognosis for cancer patients despite their tremendous side effects. Antitumor-targeted drugs and molecular diagnosis are typical examples of these attempts at novel treatment. Further innovations towards molecular biomarkers are expected to improve the prognosis of cancer patients. Cancer is considered one of the most lethal diseases worldwide. As one of the most reproducible predictors of thromboembolism, the D-dimer level is commonly considered by oncologists. Previous studies have demonstrated that the most correlated genes at the D-dimer level are F3, F5 and FGA
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