scholarly journals Construction and Validation of a Novel Pyroptosis-Related Gene Signature to Predict the Prognosis of Uveal Melanoma

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuan Cao ◽  
Jiaheng Xie ◽  
Liang Chen ◽  
Yiming Hu ◽  
Leili Zhai ◽  
...  
Keyword(s):  
Uveal Melanoma ◽  
Poor Prognosis ◽  
Tumor Recurrence ◽  
Gene Signature ◽  
Related Gene ◽  
Programmed Death ◽  
Prognosis Model ◽  
New Ideas ◽  
Full Throttle

Uveal melanoma is the most common primary intraocular tumor with a poor prognosis. Currently, treatment for UVM is limited, and the development of drug resistance and tumor recurrence are common. Therefore, it is important to identify new prognostic biomarkers of UVM and explore their role in the tumor microenvironment. Pyroptosis is a way of cell programmed death, and related research is in full throttle. However, the role of pyroptosis in UVM is unclear. In this study, we constructed the prognosis model of pyroptosis-related genes of UVM. This model can accurately guide the prognosis of UVM, and different groups differ in immune infiltration. We further verified our results in cell experiments. To some extent, our study can provide new ideas for the diagnosis and treatment of UVM.

scholarly journals Predicting the Prognosis of Esophageal Adenocarcinoma by a Pyroptosis-Related Gene Signature

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruijie Zeng ◽  
Shujie Huang ◽  
Xinqi Qiu ◽  
Zewei Zhuo ◽  
Huihuan Wu ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Poor Prognosis ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Validation Dataset ◽  
Related Gene ◽  
Independent Validation ◽  
Risk Patients ◽  
Cancer Genome Atlas

Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the signature was constructed with novel prognostic values. Moreover, the downregulation of GSDMB within the signature is notably correlated with enhanced DNA methylation. The pyroptosis-related signature might be related to the immune response and regulation of the tumor microenvironment. Several inhibitors including GDC-0879 and PD-0325901 are promising in reversing the altered differentially expressed genes in high-risk patients. Our findings provide insights into the involvement of pyroptosis in EAC progression and are promising in the risk assessment as well as the prognosis for EAC patients in clinical practice.

scholarly journals Identification of the Novel Pyroptosis-Related Gene Signature in Patients with Esophageal Adenocarcinoma

2021 ◽  
Author(s):  
Ruijie Zeng ◽  
Shujie Huang ◽  
Zewei Zhuo ◽  
Huihuan Wu ◽  
Weihong Sha ◽  
...  
Keyword(s):  
Esophageal Adenocarcinoma ◽  
Poor Prognosis ◽  
Gene Signature ◽  
The Cancer Genome Atlas ◽  
Validation Dataset ◽  
The Novel ◽  
Related Gene ◽  
Independent Validation ◽  
Cancer Genome Atlas

Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the five-gene signature was constructed with novel prognostic values. Moreover, the genes in the pyroptosis-related signature, CASP1, GSDMB, IL1B, PYCARD, and ZBP1, might be involved in immune response and regulation of the tumor microenvironment. Our findings indicate that the five-gene signature provides insights into the involvement of pyroptosis in EAC progression, and is promising in the risk assessment as well as prognosis for EAC patients in clinical practice.

scholarly journals Role of PDL1 as a prognostic marker in renal cell carcinoma: a prospective observational study in eastern India

2019 ◽  
Vol 11 ◽  
pp. 175628721986885
Author(s):  
Barun Kumar ◽  
Amlan Ghosh ◽  
Chhanda Datta ◽  
Dilip Kumar Pal
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Prognostic Marker ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Disease Recurrence ◽  
Programmed Death ◽  
Specific Mortality ◽  
Cancer Specific Mortality

Background: Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies. Programmed death ligand-1 (PDL1) is an immune checkpoint inhibitor, instrumental in ‘T cell escape’ of malignant cells. PDL1 has been shown to be associated with poor prognosis in multiple small studies. In this study, we want to study the role of PDL1 as a prognostic marker in RCC in an Indian population. Methods: A total of 30 patients who underwent radical or partial nephrectomy, with histopathological findings of RCC, were included in the study. PDL1 expression was studied in tumour tissue with immunohistochemistry. Patients were followed up for a period of 2 years for disease recurrence and cancer-specific mortality. Results: Expression of PDL1 was seen to be associated with higher grade and stage at presentation. PDL1 expression was also associated with statistically significant increased incidence of disease recurrence. Although cancer-specific mortality was higher in patients with positive PDL1 expression, it was seen to be statistically insignificant. Conclusions: PDL1 is a novel prognostic marker for RCC and is associated with poor prognosis. More studies with larger patient pool and multicentric studies will establish the role of PDL1 with certainty. This can be the torchbearer for the future management of RCC.

scholarly journals A Novel Glycolysis-related Gene Signature for Survival Prediction in Patients with Head and Neck Squamous Cell Carcinoma

2021 ◽  
Author(s):  
Haimei Qin ◽  
Junli Wang ◽  
Biyun Liao ◽  
Zhonglin Liu ◽  
Rong Wang
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Squamous Cell ◽  
Poor Prognosis ◽  
Risk Group ◽  
Gene Signature ◽  
Neck Squamous Cell Carcinoma ◽  
Related Gene ◽  
Cancer Subtypes

Abstract Background: Head and neck squamous cell carcinoma (HNSCC) is most diagnosed at an advanced stage with poor prognosis. Single gene biomarkers cannot have enough predictive ability in HNSCC. Glycolysis participating in cancers was verified. Thus, this study aimed to identify glycolysis-related gene signature predict the outcome of HNSCC. Methods: The mRNA expression data of HNSCC downloaded The Cancer Genome Atlas (TCGA) project was analyzed by Gene Set Enrichment Analysis (GSEA). We use the Cox proportional regression model to construct a prognostic model. Kaplan–Meier and receiver operating characteristic (ROC) curves were employed to estimate the signature. We also analyzed the relationship of the signature and cancer subtypes. Results: We identified nine glycolysis-related genes including G6PD, EGFR, ALDH2, GPR87, STC2, PDK3, ELF3, STC1 and GNPDA1 as prognosis-related genes signature in HNSCC. HNSCC patients were divided into high and low risk group according to the signature. High risk group showed more poor prognosis and the risk score can precisely predict the prognosis of HNSCC. Additionally, the signature also can be used in cancer subtypes. Conclusion: This study established the 9-mRNA glycolysis signature which may serve as a prospective biomarker for prognosis and novel treatment target in HNSCC.

scholarly journals Prognostic Role of Programmed Death Ligand-1 on Tumor-Infiltrating Immune Cells in “High-Risk” Patients Following Radical Cystectomy: A Retrospective Cohort Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Chung Un Lee ◽  
Dong Hyeon Lee ◽  
Wan Song
Keyword(s):  
High Risk ◽  
Radical Cystectomy ◽  
Immune Cells ◽  
Tumor Recurrence ◽  
Prognostic Role ◽  
Programmed Death Ligand 1 ◽  
High Risk Patients ◽  
Programmed Death ◽  
Risk Patients

PurposeThe aim of this study is to investigate the prognostic role of programmed death ligand-1 (PD-L1) on tumor-infiltrating immune cells (TIICs) in patients after radical cystectomy (RC) for bladder cancer (BCa).Materials and MethodsWe retrospectively reviewed 92 “high-risk” (≥pT3a and/or pN+) patients who underwent RC for BCa, without adjuvant chemotherapy (AC), between April 2014 and December 2019. PD-L1 on TIICs was measured only using the VENTANA (SP-142) immunohistochemistry assay. Patients were categorized into three groups based to the percentage of the tumor area covered by PD-L1 on TIICs: IC0 (<1%), IC1 (≥1% and <5%), and IC2/3 (≥5%). Positive PD-L1 was defined as IC2/3 (≥5%). Kaplan–Meier survival analysis was used to illustrate recurrence-free survival (RFS), and Cox proportional hazard models were used to identify predictive factors of tumor recurrence.ResultsWithin the cohort, the proportions of PD-L1 IC0, IC1, and IC2/3 were 21.7%, 23.9%, and 54.4%, respectively. At follow-up (mean 31.3 months), tumor recurrence was identified in 49 patients (53.3%). Using multivariable analysis, tumor stage (pT4; P=0.005), positive lymph nodes (P=0.021), and positive PD-L1 on TIICs (P=0.010) were independent predictors of tumor recurrence. The 2- and 3-year RFS rates were 67.7% and 64.2% in negative PD-L1 on TIICs, while 27.8% and 22.3% in positive PD-L1 on TIICs, respectively.ConclusionsPositive PD-L1 on TIICs was significantly associated with poorer RFS in “high-risk” patients after RC without AC. Our results support the use of adjuvant immunotherapy in “high-risk” patients with positive PD-L1 on TIICs after RC.

scholarly journals Identification and Validation of a Seizure-Free-Related Gene Signature for Predicting Poor Prognosis in Lower-Grade Gliomas

2021 ◽  
Vol Volume 14 ◽  
pp. 7399-7410
Author(s):  
Jinxing Li ◽  
Jing Huan ◽  
Fu Yang ◽  
Haixin Chen ◽  
Mingguang Wang ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Gene Signature ◽  
Lower Grade ◽  
Related Gene

scholarly journals Development and Validation of a Novel Mitophagy-Related Gene Prognostic Signature for Hepatocellular Carcinoma Based on Immunoscore Classification of Tumor

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Hao Chen ◽  
Jinghua Wang ◽  
Ruijie Zeng ◽  
Yujun Luo ◽  
Kehang Guo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Model ◽  
Univariate Analysis ◽  
Risk Groups ◽  
Gene Signature ◽  
Related Gene ◽  
Prognosis Model ◽  
Prognostic Prediction ◽  
Selection Operator ◽  
Functional Analyses

Emerging evidence suggested that mitophagy may play an important role in the progression of hepatocellular carcinoma (HCC), whereas the association between mitophagy-related genes and HCC patients’ prognosis remains unknown. In this study, we aimed to investigate the potential prognostic values of mitophagy-related genes (MRGs) on HCC patients at the genetic level. According to median immunoscore, we categorized HCC patients from TCGA cohort into two immune score groups, while 39 differential expression MRGs were identified. By using univariate analysis, we screened out 18 survival-associated MRGs, and then, the least absolute shrinkage and selection operator (LASSO) analysis was applied to construct a prognosis model that consisted of 9 MRGs (ATG7, ATG9A, BNIP3L, GABARAPL1, HTRA2, MAP1LC3B2, TFE3, TIGAR, and TOMM70). In our prognostic model, overall survival in the high and low-risk groups was significantly different P < 0.001 , and the respective areas under the curve (AUC) of our prognostic model were 0.686 for 3-year survival in the TCGA cohort and 0.776 for 3-year survival in the ICGC cohort. Moreover, we identified the risk score as the independent factor for predicting the HCC patients’ prognosis by using single and multifactor analyses, and a nomogram was also constructed for future clinical application. Further functional analyses showed that the immune status between two risk groups was significantly different. Our findings may provide a novel mitophagy-related gene signature, and these will be better used for prognostic prediction in HCC, thus improving patient outcome.

scholarly journals Integration of Clinical and Transcriptomics Reveals Reprogramming of the Lipid Metabolism in Gastric Cancer

2021 ◽  
Author(s):  
Yanyan Li ◽  
Jungang Zhao ◽  
Renpin Chen ◽  
Shengwei Chen ◽  
Yilun Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lipid Metabolism ◽  
Cox Regression ◽  
Gene Signature ◽  
Cancer Cell Proliferation ◽  
Related Gene ◽  
Altered Expression ◽  
Transcriptomic Data ◽  
Cellular Processes

Abstract Background: Lipid metabolism has a profound impact on gastric cancer (GC) progression and is a newly targetable vulnerability for cancer therapy. Given the importance of lipids in cancer cellular processes, in this study we employed lipidomic clinical and transcriptomic data of GC to connect the variations of lipid metabolism changes.Method: We constructed a clinical nomogram based on the lipid factors and other clinical items. Then by using multi-omics techniques, we established a lipid-related gene signature for individualized prognosis prediction in patients with GC. Moreover, a total of 1357 GC cases were then applied to evaluate the robustness of this model. WGCNA was used to identify co-expression modules and enriched genes associated with GC lipid metabolism. The role of key genes ACLY in GC was further investigated.Results: The prognostic value of the lipidomic signature was analyzed using Cox regression model, and clinical nomogram was established. Among them, we observed overexpression of ACLY significantly increased the levels of intracellular free fatty acid and triglyceride, and activate AKT/mTOR pathway to promote cancer development.Conclusions: In conclusion, our findings delineated a GC clinical and lipidomic signature and revealed that GC exhibited a reprogramming of lipid metabolism in association with an altered expression of lipid metabolism-associated genes. Among them, ACLY significantly promoted GC lipid metabolism and increased cancer cell proliferation, suggesting that this pathway can be targetable as a metabolic vulnerability in future GC therapy.

scholarly journals Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Hang Ji ◽  
Yixu Ba ◽  
Shuai Ma ◽  
Kuiyuan Hou ◽  
Shan Mi ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Prognostic Significance ◽  
Adaptive Immune Response ◽  
Gene Mutations ◽  
Gene Signature ◽  
Current Treatment ◽  
Immune Checkpoints ◽  
Related Gene ◽  
Treatment Paradigm

Interferon-gamma (IFNG) has profound impacts on tumor-immune interaction and is of great clinical significance for multiple cancers. Exploring the role of IFNG in glioblastoma (GBM) may optimize the current treatment paradigm of this disease. Here, multi-dimensional data of 429 GBM samples were collected. Various bioinformatics algorithms were employed to establish a gene signature that characterizes immunological features, genomic alterations, and clinical characteristics associated with the IFNG response. In this way, a novel IFNG-related gene signature (IFNGrGS, including TGFBI, IL4I1, ACP5, and LUM) has been constructed and validated. Samples with increased IFNGrGS scores were characterized by increased neutrophil and macrophage infiltration and exuberant innate immune responses, while the activated adaptive immune response may be frustrated by multiple immunosuppressive mechanisms. Notably, the IFNG pathway as well as its antagonistic pathways including IL4, IL10, TGF-beta, and VEGF converged on the expression of immune checkpoints. Besides, gene mutations involved in the microenvironment were associated with the IFNGrGS-based stratification, where the heterogeneous prognostic significance of EGFR mutation may be related to the different degrees of IFNG response. Moreover, the IFNGrGS score had solid prognostic value and the potential to screen ICB and radiotherapy sensitive populations. Collectively, our study provided insights into the role of IFNG on the GBM immune microenvironment and offered feasible information for optimizing the treatment of GBM.

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