BackgroundColorectal cancer (CRC) is one of the most common malignant tumors in the world. Ferroptosis is a newly defined form of cell death, distinguished by different morphology, biochemistry, and genetics, and involved in CRC progression and treatment. This study aims to establish a predictive model to elucidate the relationship between ferroptosis and prognosis of CRC patients, to explore the potential value of ferroptosis in therapeutic options.MethodsThe ferroptosis-related genes were obtained from the GeneCards and FerrDb websites. The limma R package was used to screen the differential ferroptosis-related genes (DEGs) in CRC from The Cancer Genome Atlas (TCGA) dataset. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were to establish the 10-gene prognostic signature. The survival and receiver operating characteristic (ROC) curves were illustrated to evaluate the predictive effect of the signature. Besides, independent prognostic factors, downstream functional enrichment, drug sensitivity, somatic mutation status, and immune feature were analyzed. Moreover, all these conclusions were verified by using multiple datasets in International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO).ResultsTen ferroptosis-related gene signature (TFAP2C, SLC39A8, NOS2, HAMP, GDF15, FDFT1, CDKN2A, ALOX12, AKR1C1, ATP6V1G2) was established to predict the prognosis of CRC patients by Lasso cox analysis, demonstrating a good performance on Receiver operating characteristic (ROC) and Kaplan–Meier (K–M) analyses. The CRC patients in the high- or low-risk group showed significantly different fractions of immune cells, such as macrophage cells and CD8+ T cells. Drug sensitivity and somatic mutation status like TP53 were also closely associated with the risk scores.ConclusionsIn this study, we identified a novel ferroptosis-related 10-gene signature, which could effectively predict the prognosis and survival time of CRC patients, and provide meaningful clinical implications for targeted therapy or immunotherapy. Targeting ferroptosis is a good therapeutic option for CRC patients. Further studies are needed to reveal the underlying mechanisms of ferroptosis in CRC.
Prefoldin subunits (PFDN), primarily known for co-chaperone function associated with cytoskeletal rearrangement, have been found involved in epithelial–mesenchymal transition (EMT) and cancer progression. However, studies focusing on the roles of PFDN in gastric cancer (GC) remain limited. The present study aims to evaluate the prognostic values of PFDN in GC. Prognostic roles of PFDNs were analyzed via the Kaplan–Meier platform, followed by subset analysis within various clinical parameters. High mRNA expression of PFDN2, PFDN3 and PFDN4 displayed poor overall survival (OS) while PFDN5 displayed favorable OS. In HER2+ subset, PFDN2, PFDN3, PFDN4 and PFDN6 displayed poor OS. In human epidermal growth factor receptor 2 (HER2−) subset, PFDN2, PFDN3 and PFDN4 displayed poor OS. In intestinal type subset, PFDN1 and PFDN2 displayed poor OS. In diffuse-type subset, PFDN2 and PFDN6 displayed poor OS. In moderate differentiation type subset, PFDN1 displayed poor OS. In poor differentiation type subset, PFDN2 and PFDN6 displayed poor OS. In metastasis negative subset, PFDN1, PFDN2 and PFDN6 displayed poor OS. In lymph node (LN) positive subset, PFDN2 and PFDN5 displayed poor OS. The present study provided insightful clues into the poor prognostic values of PFDNs in GC patients.
Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group ( P < 0.001 ). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.
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