scholarly journals Exploration of Key Genes Combining with Immune Infiltration Level and Tumor Mutational Burden in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Jing Chen ◽  
shuzhen wu ◽  
sijia ge ◽  
ran Ji ◽  
Yuyan Chen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Poor Prognosis ◽  
R Package ◽  
Immune Microenvironment ◽  
Chi Square ◽  
Term Survival ◽  
Immune Infiltration ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
And Function

Abstract Background: Hepatocellular carcinoma (HCC) is still a lethal malignancy because of its heterogenicity and aggressive behavior, with unsatisfactory early diagnosis and poor prognosis. Recently, few somatic mutations have been reported to associated with HCC carcinogenesis and function in predicting HCC progression. Interactions of tumor cells with surrounding immune microenvironment in HCC participate in orchestrating the onset and development. Herein, our aim is to investigate the associations of tumor mutational burden (TMB) with immune microenvironment in HCC. Then we will seek for differential expression genes (DEGs) in terms of immune and TMB scores and discuss whether their latent functions affect HCC prognosis and progression.Methods: The expression, clinical and mutational data were downloaded from TCGA database, then calculated the immune infiltration of these HCC samples by R package “ssGSEA”, “CIBERSORT” and “ESTIMATE”. Then the samples were clarified to 2 groups according to the immune levels. TMB was also calculated and differential expressional genes (DEGs) in the low and high TMB group were intersected and the different immune level groups. Then the cox analyses and prognostic model were performed and tested by R package “glmnet”. Then the selected genes BCL10 and TRAF3 were tested their expression by qrt-PCR and IHC and tested their clinical correlation by chi-square analyses and their biological processes enriched by GSEA, and their immune infiltration by “ssGSEA” individualy. Last, pearson algorithm was employed to judge the relevance of BCL10 and TRAF3.Results: Upregulated degrees of immune infiltration correlated with TMB, they synergistically predicted poor prognosis in HCC. DEGs enriched in immune-related pathways could serve as an indicator of therapeutic effect of HCC immunotherapy. Among these DEGs, BCL10 and TRAF3 were highly expressed in HCC tissues, especially in TP53 mutation group. BCL10 and TRAF3 corporately exhibited immunological function, thereby affecting HCC progression and prognosis.Conclusions: We identified that BCL10 and TRAF3 exhibited good prognostic value in predicting the clinical outcome of HCC patients, which may influence TMB and tumor microenvironment (TME) and help us moving towards immune-based therapies with HCC patients, ultimately improving their long-term survival.

scholarly journals A novel panel based on immune infiltration and tumor mutational burden for prognostic prediction in hepatocellular carcinoma

Aging ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 8563-8587
Author(s):  
Chan Xie ◽  
Hewei Wu ◽  
Tao Pan ◽  
Xingrong Zheng ◽  
Xiaoan Yang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Infiltration ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Prognostic Prediction

Comprehensive exploration of tumor mutational burden and immune infiltration in diffuse glioma

2021 ◽  
Vol 96 ◽  
pp. 107610
Author(s):  
Kai Kang ◽  
Fucun Xie ◽  
Yijun Wu ◽  
Zhile Wang ◽  
Li Wang ◽  
...  
Keyword(s):  
Diffuse Glioma ◽  
Immune Infiltration ◽  
Mutational Burden ◽  
Tumor Mutational Burden

scholarly journals Identification of Biomarkers Related to Immune Cell Infiltration in Hepatocellular Carcinoma Using Gene Co-Expression Network

2021 ◽  
Vol 27 ◽  
Author(s):  
Wanbang Zhou ◽  
Yiyang Chen ◽  
Ruixing Luo ◽  
Zifan Li ◽  
Guanwei Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Network Analysis ◽  
Tumor Progression ◽  
Protein Interactions ◽  
Immune Cells ◽  
Immune Cell ◽  
Immune Microenvironment ◽  
Hub Genes ◽  
Expression Levels ◽  
Immune Infiltration

Hepatocellular carcinoma (HCC) is a common cancer with poor prognosis. Due to the lack of effective biomarkers and its complex immune microenvironment, the effects of current HCC therapies are not ideal. In this study, we used the GSE57957 microarray data from Gene Expression Omnibus database to construct a co-expression network. The weighted gene co-expression network analysis and CIBERSORT algorithm, which quantifies cellular composition of immune cells, were used to identify modules related to immune cells. Four hub genes (EFTUD2, GAPDH, NOP56, PA2G4) were identified by co-expression network and protein-protein interactions network analysis. We examined these genes in TCGA database, and found that the four hub genes were highly expressed in tumor tissues in multiple HCC groups, and the expression levels were significantly correlated with patient survival time, pathological stage and tumor progression. On the other hand, methylation analysis showed that the up-regulation of EFTUD2, GAPDH, NOP56 might be due to the hypomethylation status of their promoters. Next, we investigated the correlations between the expression levels of four hub genes and tumor immune infiltration using Tumor Immune Estimation Resource (TIMER). Gene set variation analysis suggested that the four hub genes were associated with numerous pathways that affect tumor progression or immune microenvironment. Overall, our results showed that the four hub genes were closely related to tumor prognosis, and may serve as targets for treatment and diagnosis of HCC. In addition, the associations between these genes and immune infiltration enhanced our understanding of tumor immune environment and provided new directions for the development of drugs and the monitoring of tumor immune status.

scholarly journals Elevated Preoperative Serum CA19-9 Levels in Patients with Hepatocellular Carcinoma Is Associated with Poor Prognosis after Resection

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Yu-Ling Chen ◽  
Chien-Hung Chen ◽  
Rey-Heng Hu ◽  
Ming-Chih Ho ◽  
Yung-Ming Jeng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Tumor Size ◽  
Poor Prognosis ◽  
Characteristic Curve ◽  
Tumor Grade ◽  
Serum Levels ◽  
Tumor Stage ◽  
High Serum ◽  
Term Survival ◽  
Preoperative Serum

Serum levels of the tumor marker CA19-9 have been reported to be elevated in patients with hepatocellular carcinoma (HCC), but its clinicopathologic significance is still unknown. A cohort of 304 patients undergoing surgical resection for HCC and having preoperative CA19-9 data was enrolled in this study. Serum CA19-9 levels were correlated with clinicopathologic factors. Univariate and multivariate analyses were performed to determine the predictors of patient survival. On receiver operating characteristic curve analysis, the cut off value of CA19-9 was determined to be 27 U/mL. One hundred and six patients had preoperative CA19-9 values >27 U/mL. High serum CA19-9 levels did not correlate with patient age, sex, viral status,α-fetoprotein level, tumor size, tumor grade, tumor stage, multiplicity, and vascular invasion. Patients with elevated preoperative CA19-9 levels had lower 10-year survival than those without CA19-9 elevation. Multivariate analysis revealed that CA19-9 level, tumor grade, and tumor size are independent prognostic factors for long-term survival. In conclusion, a preoperative CA19-9 value >27 U/mL is associated with poor prognosis after resection for HCC.

Immune microenvironment features and efficacy of PD-1/PD-L1 blockade in non-small cell lung cancer (NSCLC) patients with EGFR or HER2 exon 20 insertions.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21540-e21540 ◽  
Author(s):  
Kaiyan Chen ◽  
Guoqiang Pan ◽  
Yanjun Xu ◽  
Yun Fan
Keyword(s):  
Tumor Infiltrating Lymphocytes ◽  
Small Cell Lung ◽  
Immune Microenvironment ◽  
Limited Efficacy ◽  
Mutational Burden ◽  
Tumor Mutational Burden ◽  
Exon 20 ◽  
Nsclc Patients ◽  
L1 Protein ◽  
Infiltrating Lymphocytes

e21540 Background: This study aimed to investigate the immune microenvironment features and efficacy of PD-1/PD-L1 blockade of NSCLC with insertions in exon 20 (Ex20ins) of EGFR or HER2. Methods: Molecular spectrum, tumor mutational burden (TMB), PD-L1 protein expression, and the abundance of CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were reviewed for NSCLC patients with Ex20ins of EGFR or HER2. Results: Thirty-five patients carrying EGFR Ex20ins and 21 patients harboring HER2 Ex20ins were retrospectively enrolled between April 2016 and September 2018. The average TMB was 3.3 mutations/megabase. PD-L1 expression in patients with EGFR Ex20ins was significantly higher than those with HER2 mutations (48.6% vs. 19.0%, P=0.027). High TMB and PD-L1 expression was independently associated with considerably poor prognosis (P=0.025, P=0.045; respectively). Finally, patients harboring EGFR Ex20ins seemed to be sensitive to PD-1/PD-L1 blockage whereas it showed limited efficacy in patients with HER2 Ex20ins. Conclusions: NSCLC patients with EGFR/ HER2 Ex20ins had distinct immune features. Patients with EGFR Ex20ins had significantly higher PD-L1 expression than those with HER2 mutations, which may be the underlying reason for the different responses to PD-1/PD-L1 blockage.

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