Abstract
BackgroundFerroptosis is a newly defined form of programmed cell death that plays an important role in many cancers. However, ferroptosis-related lncRNAs (FRLs) involved in the regulation of colon cancer are not thoroughly understood. This study aimed to identify a prognostic FRL signature in colon cancer and explore its potential molecular function.MethodsRNA-seq data and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database, and a list of ferroptosis-related genes was extracted from the FerrDb website. Analysis of differentially expressed FRLs was performed using the ‘limma’ package in R software. By implementing coexpression analysis and univariate Cox analysis, we then identified prognostic FRLs. Using Cox regression analysis with the least absolute shrinkage and selection operator (LASSO) algorithm, we constructed a prognostic model based on 4 FRLs. We evaluated the prognostic power of this model using Kaplan–Meier (K-M) survival curve analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between the signature and immune landscape, somatic mutation and drug sensitivity were explored. Finally, in vitro experiments were conducted to validate the functions of AP003555.1 and AC000584.1.ResultsA 4-FRL signature was constructed. Two risk groups were classified based on the risk score calculated by this signature. The signature-based risk score exhibited a more powerful capacity for survival prediction than traditional clinicopathological features in colon patients. Additionally, we observed a significant difference in immune cells, such as CD4+ and CD8+ T cells and macrophages, between the two groups. Moreover, the high-risk group exhibited lower IC50 values for certain chemotherapy drugs, such as cisplatin, docetaxel, bleomycin or axitinib. Finally, the in vitro experiments showed that ferroptosis processes were suppressed after AP003555.1 and AC000584.1 knockdown.ConclusionThe proposed 4-FRL signature is a promising biomarker to predict clinical outcomes and therapeutic responses in colon cancer patients.
Highlights
Colon cancer is the third most-diagnosed cancer and the second leading cause of cancer-related deaths in the world
RNA sequencing (RNA-seq) data and relevant clinical information were obtained from The Cancer Genome Atlas (TCGA) database, and a list of ferroptosis-related genes was extracted from the FerrDb website
The in vitro experiments showed that ferroptosis processes were suppressed after AP003555.1 and AC000584.1 knockdown
Summary
Colon cancer is the third most-diagnosed cancer and the second leading cause of cancer-related deaths in the world. According to the latest online epidemiological database, there were more than 1.9 million new colon cancer cases in 2020, and 0.9 million deaths were recorded in the same year [2]. Even with the rapid development of cancer screening methods, many patients are diagnosed at an advanced stage with multiple symptoms, such as haematochezia or colonic obstruction [2]. There are only a few effective therapeutic targets for colon cancer patients [3]. Ferroptosis-related lncRNAs (FRLs) involved in the regulation of colon cancer are not thoroughly understood. This study aimed to identify a prognostic FRL signature in colon cancer and explore its potential molecular function
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