scholarly journals Analysis of Threshold Change of Tumor Mutation Burden in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xinwei He ◽  
Ming Yu ◽  
Xuezhong Wang ◽  
Jixian Chen ◽  
Xianglin Li
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Expression Level ◽  
Surgical Removal ◽  
Tumor Mutation Burden ◽  
Low Level ◽  
Mutation Burden ◽  
Drinking History ◽  
High Level ◽  
Level Group

Background. The purpose of this study was to investigate the change of tumor mutation burden (TMB) in gastric cancer (GC) and its relationship with prognosis. Methods. A total of 262 patients with GC from January 2018 to December 2019 were included in this study. All patients were in the advanced stage and were treated with surgical removal of D2 lymph nodes and dissection. Clinical data and gene expression profile data of the GC dataset in The Cancer Genome Atlas were collected. Patients were randomly divided into a high-level group and a low-level group according to the TMB of 8 mutations/Mb. TMB of GC was calculated based on cell mutation data. Cox regression model was used to evaluate the relationship between TMB and prognosis of GC patients. Results. The total mutation rate of 262GC patients was 92.85%. The top 5 mutant genes were TP53, RB1, ARID1A, KMT2B, and RET. The expression level of TMB in GC patients was statistically significant with age, drinking history, and differentiation type. 94 of the 262 patients died, and 168 survived during the follow-up period. Patients with a high level of TMB had a worse prognosis than those with low level of TMB. The results of univariate and multivariate logistic analysis showed that the overall survival rate of GC patients was statistically significant with age, drinking history, clinical stage, differentiation type, and TMB. Conclusion. GC patients are often accompanied by changes in TMB, and its expression level is closely related to the degree of pathological differentiation, which is an independent factor affecting the prognosis of GC patients. High TMB value can evaluate the prognosis and provide a reference for the formulation of clinical treatment plans for GC patients.

scholarly journals Significance of Tumor Mutation Burden Combined With Immune Infiltrates in the Progression and Prognosis of Advanced Gastric Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiong Guo ◽  
Xiaolong Liang ◽  
Yujun Wang ◽  
Anqi Cheng ◽  
Han Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Visual Analysis ◽  
Risk Model ◽  
Cox Regression ◽  
Expression Patterns ◽  
Clinicopathological Parameters ◽  
Tumor Mutation Burden ◽  
Cox Regression Analysis ◽  
Mutation Burden

Gastric cancer (GC) is a serious malignant tumor with high mortality and poor prognosis. The prognosis and survival are much worse for advanced gastric cancer (AGC). Recently, immunotherapy has been widely promoted for AGC patients, and studies have shown that tumor mutation burden (TMB) is closely related to immunotherapy response. Here, RNA-seq data, matched clinical information, and MAF files were downloaded from the cancer genome atlas (TCGA)-STAD project in the TCGA database. The collation and visual analysis of mutation data were implemented by the “maftools” package in R. We calculated the TMB values for AGC patients and divided the patients into high- and low-TMB groups according to the median value of TMB. Then, the correlation between high or low TMB and clinicopathological parameters was calculated. Next, we examined the differences in gene expression patterns between the two groups by using the “limma” R package and identified the immune-related genes among the DEGs. Through univariate Cox regression analysis, 15 genes related to prognosis were obtained. Furthermore, the two hub genes (APOD and SLC22A17) were used to construct a risk model to evaluate the prognosis of AGC patients. ROC and survival curves and GEO data were used as a validation set to verify the reliability of this risk model. In addition, the correlation between TMB and tumor-infiltrating immune cells was examined. In conclusion, our results suggest that AGC patients with high TMB have a better prognosis. By testing the patient’s TMB, we could better guide immunotherapy and understand patient response to immunotherapy.

scholarly journals Comprehensive analysis of genomic mutation signature and tumor mutation burden for prognosis of intrahepatic cholangiocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Rui Zhang ◽  
Qi Li ◽  
Jialu Fu ◽  
Zhechuan Jin ◽  
Jingbo Su ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Cox Regression ◽  
Tnm Stage ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Tumor Mutation Burden ◽  
Kaplan Meier ◽  
Mutation Burden ◽  
Significant Difference ◽  
Genomic Mutation

Abstract Background Intrahepatic cholangiocarcinoma (iCCA) is a highly lethal malignancy of the biliary tract. Analysis of somatic mutational profiling can reveal new prognostic markers and actionable treatment targets. In this study, we explored the utility of genomic mutation signature and tumor mutation burden (TMB) in predicting prognosis in iCCA patients. Methods Whole-exome sequencing and corresponding clinical data were collected from the ICGC portal and cBioPortal database to detect the prognostic mutated genes and determine TMB values. To identify the hub prognostic mutant signature, we used Cox regression and Lasso feature selection. Mutation-related signature (MRS) was constructed using multivariate Cox regression. The predictive performances of MRS and TMB were assessed using Kaplan–Meier (KM) analysis and receiver operating characteristic (ROC). We performed a functional enrichment pathway analysis using gene set enrichment analysis (GSEA) for mutated genes. Based on the MRS, TMB, and the TNM stage, a nomogram was constructed to visualize prognosis in iCCA patients. Results The mutation landscape illustrated distributions of mutation frequencies and types in iCCA, and generated a list of most frequently mutated genes (such as Tp53, KRAS, ARID1A, and IDH1). Thirty-two mutated genes associated with overall survival (OS) were identified in iCCA patients. We obtained a six-gene signature using the Lasso and Cox method. AUCs for the MRS in the prediction of 1-, 3-, and 5-year OS were 0.759, 0.732, and 0.728, respectively. Kaplan–Meier analysis showed a significant difference in prognosis for patients with iCCA having a high and low MRS score (P < 0.001). GSEA was used to show that several signaling pathways, including MAPK, PI3K-AKT, and proteoglycan, were involved in cancer. Conversely, survival analysis indicated that TMB was significantly associated with prognosis. GSEA indicated that samples with high MRS or TMB also showed an upregulated expression of pathways involved in tumor signaling and the immune response. Finally, the predictive nomogram (that included MRS, TMB, and the TNM stage) demonstrated satisfactory performance in predicting survival in patients with iCCA. Conclusions Mutation-related signature and TMB were associated with prognosis in patients with iCCA. Our study provides a valuable prognostic predictor for determining outcomes in patients with iCCA.

scholarly journals Expression of LOX Suggests Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p &lt; 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

Overexpression of a novel oncogene Cadherin 6 correlates with tumor progression and poor prognosis in gastric cancer

2021 ◽  
Author(s):  
Zongxian Zhao ◽  
Shuliang Li ◽  
Shilong Li ◽  
Jun Wang ◽  
Hai Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Roc Curve ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Diagnostic Efficiency ◽  
Gastric Tissue ◽  
Diagnosis And Prognosis ◽  
T Classification

Abstract BackgroundGastric cancer (GC) is one of the most common and fatal cancers worldwide and effective biomarkers aids in GC management and prognosis. Hence, we explored the role and function of cadherin 6 (CDH6) in diagnosis and prognosis of gastric cancer. MethodsThe expression level of CDH6 in GC tissue and normal gastric tissue were analyzed using multiple public databases. Gene set enrichment analysis (GSEA) was performed using The Cancer Genome Atlas dataset (TCGA). The diagnostic efficiency of CDH6 expression in GC patients was determined through receiver operating characteristic (ROC) curve analysis. The associations between clinical variables and expression of CDH6 were evaluated statistically and the prognostic factors for overall survival were analyzed by univariate and multivariate Cox regression. Forty-four GC tissues, corresponding adjacent normal tissues (n=20), and detailed clinical information were collected from Tianjin Medical University General Hospital, CDH6 expression level was detected for further validation. ResultsCDH6 was upregulated in GC samples compared with normal gastric tissue, and GSEA identified the citrate cycle tricarboxylic (TCA) cycle, extracellular matrix (ECM) receptor interaction, glyoxylate and dicarboxylate metabolism oxidative phosphorylation, and pentose phosphate pathway as differentially enriched in GCs. According to the area under the ROC curve (AUC) (AUC=0.829 in TCGA and 0.966 in GSE54129), CDH6 had high diagnostic efficiency. Patients with high expression of CDH6 was associated with higher T classification and worse prognoses than those with low CDH6 expression in GC. Univariate and multivariate Cox regression analysis showed that CDH6 was an independent risk factor for overall survival (univariate: HR = 1.305, P = 0.002, multivariate: HR = 1.481, P < 0.001). ConclusionCDH6 was upregulated in GC and high CDH6 expression indicated higher T classification and worse prognoses. CDH6 could be a potentially independent molecular biomarker for diagnosis and prognosis of GC.

Minimal Residual Disease Status at Day +100 Post Allogeneic Hematopoietic Stem Cell Transplantation Is a Powerful Predictor for Post-Transplant Outcome In Patients with High Risk Acute Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3550-3550
Author(s):  
XiaoWen Tang ◽  
Xingwei Sun ◽  
Shengli Xue ◽  
Xiaolan Shi ◽  
Mingqing Zhu ◽  
...  
Keyword(s):  
High Risk ◽  
Residual Disease ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Low Level ◽  
High Level Group ◽  
Risk Patients ◽  
High Level ◽  
Level Group

Abstract Abstract 3550 Background and Objectives Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still a major cause for the failure in treatment. It has been shown that there was a closely relationship between the level of minimal residual disease (MRD) and relapse in acute leukemia (AL) patients; However, the application of multiparameter flow cytometry (MFC) for MRD assessment in high risk patients with AL who undergoing allo-HSCT is little concerned. We retrospectively analysed the serial results of MRD of 52 high risk patients with AL to evaluates the prognostic value of MRD pre and post transplantation. Methods 52 patients with a median age of 29 (13–55) years have been enrolled on this study in our hospital from January 2003 to September 2008.Diagnoses included AML (n=27) and ALL (n=25). The patients had been analyzed retrospectively the level of MRD pre-(day-30)and post-HSCT(day+30 and +100)using three color FCM with CD45/SSC gating and a comprehensive panel of monoclonal antibodies, at least one leukemia associated aberrant immunophenotype (LAIP) at diagnosis. According to the cutoff value 0.1%, two groups were defined based on the level of patient's MRD level< (low level group) or >= (high level group) 0.1%. Results The median follow up were 23 (range 1–60) months. 1.MRD level declines significantly (P=0.03) post transplant. 2. There were significantly difference between low level and high level group at day -30 before transplant with 3 years event free survival(EFS) and relapse free survival (RFS)(77.4% and 88.4% vs. 22.3% and 25.7%, p=0.007and p=0.001 respectively). 3. Concerning about MRD at day +100 after transplant, outcome was significantly better among patients with low level MRD group versus high group including 3 years OS,EFS and RFS(84.2%, 79.5% and 89.5% versus 22.9%, 9.5% and 11.2%).4. The median time from high level MRD detected first time to clinical relapse was 2.5 (range from 1 to 33) months in relapsed patients. 5. The patients with cGVHD had better 3 years OS and EFS than that without cGVHD(86.3% vs 12.1%, p<0.001 and 65.3% vs.14.8%, p< 0.001 respectively). 6. Multivariate Cox regression analysis revealed that MRD on day +100 as well as chronic GVHD were independent parameters predictive for OS and EFS. Conclusions MRD monitoring pre- and post-transplant is an important tool to predict the outcome of transplantation for patients with high risk AL. The MRD check point at day +100 should be considered crucial for subsequent therapeutic decisions after allogeneic transplantation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Nan Zhang ◽  
Peiyu Li ◽  
Xin Wu ◽  
Shaoyou Xia ◽  
Xudong Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Pearson Correlation ◽  
Disease Free Survival ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
D2 Lymph Node Dissection ◽  
Logistic Analysis ◽  
Mutation Burden ◽  
Disease Free

Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.

scholarly journals Identification of Prognostic Biomarkers of Cutaneous Melanoma Based on Analysis of Tumor Mutation Burden

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jiaqiong Lin ◽  
Yan Lin ◽  
Zena Huang ◽  
Xiaoyong Li
Keyword(s):  
Cutaneous Melanoma ◽  
Prognostic Model ◽  
Cox Regression ◽  
Risk Group ◽  
Predictive Biomarkers ◽  
Tumor Mutation Burden ◽  
Skin Development ◽  
Cox Regression Analysis ◽  
Immune Infiltration ◽  
Mutation Burden

Background. Immunotherapy offers a novel approach for the treatment of cutaneous melanoma, but the clinical efficiency varies for individual patients. In consideration of the high cost and adverse effects of immunotherapy, it is essential to explore the predictive biomarkers of outcomes. Recently, the tumor mutation burden (TMB) has been proposed as a predictive prognosticator of the immune response. Method. RNA-seq and somatic mutation datasets of 472 cutaneous melanoma patients were downloaded from The Cancer Genome Atlas (TCGA) database to analyze mutation type and TMB. Differently expressed genes (DEGs) were identified for functional analysis. TMB-related signatures were identified via LASSO and multivariate Cox regression analysis. The association between mutants of signatures and immune cells was evaluated from the TIMER database. Furthermore, the Wilcox test was applied to assess the difference in immune infiltration calculated by the CIBERSORT algorithm in risk groupings. Results. C>T substitutions and TTN were the most common SNV and mutated gene, respectively. Patients with low TMB presented poor prognosis. DEGs were mainly implicated in skin development, cell cycle, DNA replication, and immune-associated crosstalk pathways. Furthermore, a prognostic model consisting of eight TMB-related genes was developed, which was found to be an independent risk factor for treatment outcome. The mutational status of eight TMB-related genes was associated with a low level of immune infiltration. In addition, the immune infiltrates of CD4+ and CD8+ T cells, NK cells, and M1 macrophages were higher in the low-risk group, while those of M0 and M2 macrophages were higher in the high-risk group. Conclusion. Our study demonstrated that a higher TMB was associated with favorable survival outcome in cutaneous melanoma. Moreover, a close association between prognostic model and immune infiltration was identified, providing a new potential target for immunotherapy.

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