Project description:BackgroundWith the improvement of clinical treatment outcomes in diffuse large B cell lymphoma (DLBCL), the high rate of relapse in DLBCL patients is still an established barrier, as the therapeutic strategy selection based on potential targets remains unsatisfactory. Therefore, there is an urgent need in further exploration of prognostic biomarkers so as to improve the prognosis of DLBCL.MethodsThe univariable and multivariable Cox regression models were employed to screen out gene signatures for DLBCL overall survival (OS) prediction. The differential expression analysis was used to identify representative genes in high-risk and low-risk groups, respectively, where student t test and fold change were implemented. The functional difference between the high-risk and low-risk groups was identified by the gene set enrichment analysis.ResultsWe conducted a systematic data analysis to screen the candidate genes significantly associated with OS of DLBCL in three NCBI Gene Expression Omnibus (GEO) datasets. To construct a prognostic model, five genes (CEBPA, CYP27A1, LST1, MREG, and TARP) were then screened and tested using the multivariable Cox model and the stepwise regression method. Kaplan-Meier curve confirmed the good predictive performance of this five-gene Cox model. Thereafter, the prognostic model and the expression levels of the five genes were validated by means of an independent dataset. High expression levels of these five genes were significantly associated with favorable prognosis in DLBCL, both in training and validation datasets. Additionally, further analysis revealed the independent value and superiority of this prognostic model in risk prediction. Functional enrichment analysis revealed some vital pathways responsible for unfavorable outcome and potential therapeutic targets in DLBCL.ConclusionWe developed a five-gene Cox model for the clinical outcome prediction of DLBCL patients. Meanwhile, potential drug selection using this model can help clinicians to improve the clinical practice for the benefit of patients.

Project description:Background: In recent years, immunotherapy has changed the therapeutic landscape of hepatocellular carcinoma (HCC). Since the efficacy of immunotherapy is closely related to the tumor microenvironment (TME), in this study, we constructed a prognostic model based on TME to predict the prognosis and immunotherapy effect of HCC patients. Methods: Transcriptome and follow-up data of 374 HCC patients were acquired from the TCGA Cancer Genome Atlas (TCGA) database. The immune/stromal/estimate scores (TME scores) and tumor purity were calculated using the ESTIMATE algorithm and the module most associated with TME scores were screened by the weighted gene co-expression network analysis (WGCNA). A TME score-related prognostic model was constructed and patients were divided into a high-risk group and a low-risk group. Kaplan-Meier survival curves and receiver operator characteristic curve (ROC) were used to evaluate the performance of the TME risk prognostic model and validated with the external database International Cancer Genome Consortium (ICGC) cohort. Combined with clinicopathologic factors, a prognostic nomogram was established. The nomogram's ability to predict prognosis was assessed by ROC, calibration curve, and the decision curve analysis (DCA). Gene Set Enrichment Analyses (GSEA) were conducted to explore the underlying biological functions and pathways of this risk signature. Moreover, the possible correlation of risk signature with TME immune cell infiltration, immune checkpoint inhibitor (ICI) treatment response, single-nucleotide polymorphisms (SNPs), and drug sensitivity were assessed. Finally, real-time PCR was used to verify the gene expression levels in normal liver cells and cancer cells. Results: KM survival analysis results indicated that high immune/stromal/estimate score groups were closely associated with a better prognosis, while the tumor purity showed a reverse trend (p < 0.01). WGCNA demonstrated that the yellow module was significantly correlated with the TME score. The 5-genes TME risk signature was built to predict the prognosis of patients with HCC including DAB2, IL18RAP, RAMP3, FCER1G, and LHFPL2. Patients with a low-risk score have higher levels of tumor-infiltrating immune cells and higher expression of immune checkpoints, which may be more sensitive to immunotherapy. Conclusion: It provided a theoretical basis for predicting the prognosis and personalized treatment of patients with HCC.

Dataset Information

Identification and Validation of a Prognostic Gene Signature for Diffuse Large B-Cell Lymphoma Based on Tumor Microenvironment-Related Genes.

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