Combination of tumor mutation burden and immune infiltrates for the prognosis of lung adenocarcinoma

2021 ◽  
Vol 98 ◽  
pp. 107807
Author(s):  
Zhenyu Zhao ◽  
Boxue He ◽  
Qidong Cai ◽  
Pengfei Zhang ◽  
Xiong Peng ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Tumor Mutation Burden ◽  
Mutation Burden

scholarly journals Paired analysis of tumor mutation burden for lung adenocarcinoma and associated idiopathic pulmonary fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yasuto Yoneshima ◽  
Eiji Iwama ◽  
Shingo Matsumoto ◽  
Taichi Matsubara ◽  
Testuzo Tagawa ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Lung Adenocarcinoma ◽  
Genetic Alterations ◽  
Driver Mutations ◽  
Somatic Variant ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
And Oxidative Stress

AbstractGenetic alterations underlying the development of lung cancer in individuals with idiopathic pulmonary fibrosis (IPF) have remained unclear. To explore whether genetic alterations in IPF tissue contribute to the development of IPF-associated lung cancer, we here evaluated tumor mutation burden (TMB) and somatic variants in 14 paired IPF and tumor samples from patients with IPF-associated lung adenocarcinoma. We also determined TMB for 22 samples of lung adenocarcinoma from patients without IPF. TMB for IPF-associated lung adenocarcinoma was significantly higher than that for matched IPF tissue (median of 2.94 vs. 1.26 mutations/Mb, P = 0.002). Three and 102 somatic variants were detected in IPF and matched lung adenocarcinoma samples, respectively, with only one pair of specimens sharing one somatic variant. TMB for IPF-associated lung adenocarcinoma was similar to that for lung adenocarcinoma samples with driver mutations (median of 2.94 vs. 2.51 mutations/Mb) and lower than that for lung adenocarcinoma samples without known driver mutations (median of 2.94 vs. 5.03 mutations/Mb, P = 0.130) from patients without IPF. Our findings suggest that not only the accumulation of somatic mutations but other factors such as inflammation and oxidative stress might contribute to the development and progression of lung cancer in patients with IPF.

Exploration of Tumor Mutation Burden Combined with Immune Infiltrates in the Prognosis of Lung Adenocarcinoma

2021 ◽  
Author(s):  
Zhenyu Zhao ◽  
Boxue He ◽  
Qidong Cai ◽  
Pengfei Zhang ◽  
Xiong Peng ◽  
...  
Keyword(s):  
High Risk ◽  
Lung Adenocarcinoma ◽  
Clinical Application ◽  
Risk Group ◽  
High Risk Group ◽  
Immune Microenvironment ◽  
Tumor Mutation Burden ◽  
Immune Signature ◽  
Immune Infiltration ◽  
Mutation Burden

Abstract Background: Lung adenocarcinoma (LUAD) accounts for a majority of cancer-related deaths worldwide annually. A recent study shows that immunotherapy is an effective method of LUAD treatment, and tumor mutation burden (TMB) was associated with the immune microenvironment and affected the immunotherapy. Exploration of the gene signature associated with tumor mutation burden and immune infiltrates in predicting prognosis in lung adenocarcinoma in this study, we explored the correlation of TMB with immune infiltration and prognosis in LUAD.Materials and Methods: In this study, we firstly got mutation data and LUAD RNA-Seq data of the LUAD from The Cancer Genome Atlas (TCGA), and according to the TMB we divided the patients into high/low-TMB levels groups. The gene ontology (GO) pathway enrichment analysis and KOBAS-Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis were utilized to explore the molecular function of the differentially expressed genes (DEGs) between the two groups. The function enrichment analyses of DEGs were related to the immune pathways. Then, the ESTIMATE algorithm, CIBERSORT, and ssGSEA analysis were utilized to identify the relationship between TMB subgroups and immune infiltration. According to the results, Venn analysis was utilized to select the immune-related genes in DEGs. Univariate and Lasso Cox proportional hazards regression analyses were performed to construct the signature which positively associated with the immune infiltration and affected the survival. Finally, we verified the correlation between the signature and immune infiltration. Result: The exploration of the immune infiltration suggested that high-TMB subgroups positively associated with the high level of immune infiltration in LUAD patients. According to the TMB-related immune signature, the patients were divided into High/Low-risk groups, and the high-risk group was positively associated with poor prognostic. The results of the PCA analysis confirmed the validity of the signature. We also verified the effectiveness of the signature in GSE30219 and GSE72094 datasets. The ROC curves and C-index suggested the good clinical application of the TMB-related immune signature in LUAD prognosis. Another result suggested that the patients of the high-risk group were positively associated with higher TMB levels, PD-L1expression, and immune infiltration levels.Conclusion: In conclusion, our signature provides potential biomarkers for studying aspects of the TMB in LUAD such as TMB affected immune microenvironment and prognosis. This signature may provide some biomarkers which could improve the biomarkers of PD-L1 immunotherapy response and were inverted for the clinical application of the TMB in LUAD. LUAD male patients with higher TMB-levels and risk scores may benefit from immunotherapy. The high-risk patients along with higher PD-L1 expression of the signature may suitable for immunotherapy and improve their survival by detecting the TMB of LUAD.

scholarly journals The prognostic value of tumor mutation burden in EGFR-mutant advanced lung adenocarcinoma, an analysis based on cBioPortal data base

2019 ◽  
Vol 11 (11) ◽  
pp. 4507-4515 ◽  
Author(s):  
Xiao-Dong Jiao ◽  
Xi He ◽  
Bao-Dong Qin ◽  
Ke Liu ◽  
Ying Wu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Data Base ◽  
Prognostic Value ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Egfr Mutant

Common driver mutations and smoking history affect tumor mutation burden in lung adenocarcinoma

2018 ◽  
Vol 230 ◽  
pp. 181-185 ◽  
Author(s):  
Masayuki Nagahashi ◽  
Seijiro Sato ◽  
Kizuki Yuza ◽  
Yoshifumi Shimada ◽  
Hiroshi Ichikawa ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Smoking History ◽  
Driver Mutations ◽  
Tumor Mutation Burden ◽  
Mutation Burden

scholarly journals Comprehensive Analysis of the Autophagy-dependent Ferroptosis-related Gene FANCD2 in Lung Adenocarcinoma

2021 ◽  
Author(s):  
Huikai Miao ◽  
Qiannan Ren ◽  
Hongmu Li ◽  
Mingyue Zeng ◽  
Dongni Chen ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Real Time Pcr ◽  
Expression Level ◽  
Related Gene ◽  
Quantitative Real Time Pcr ◽  
Immune Microenvironment ◽  
Chemotherapy Sensitivity ◽  
Tumor Mutation Burden ◽  
Immunohistochemistry Staining ◽  
Mutation Burden

Abstract Background. The development of lung adenocarcinoma (LUAD) involves the interactions between cell proliferation and death. Autophagy-dependent ferroptosis, a distinctive cell death process was implicated in a multitude of diseases, whereas no research revealing the relationship between autophagy-dependent ferroptosis and LUAD pathogenesis was reported. Thus, the primary objective was to explore the role and potential function of the autophagy-dependent ferroptosis-related genes in LUAD.Methods. Clinical information and transcriptome profiling of patients with LUAD were retrieved and downloaded from open-source databases. Autophagy-dependent ferroptosis-related genes were screened by published articles. The key gene was identified as the intersection between the differentially expressed genes and prognosis-related genes. Patients were divided into high- and low-risk groups using the expression level of the key gene. The validity of the key gene prognosis model was verified by survival analysis. The correlation between the clinical characteristics of LUAD and the expression level of the key gene was analyzed to explore the clinical significance and prognosis value. And the roles of the key gene in response to chemotherapy, immune microenvironment and tumor mutation burden were predicted. The validation of key gene expression levels were further performed by quantitative real-time PCR and immunohistochemistry staining.Results. FANCD2, a key autophagy-dependent ferroptosis-related gene by searching database, was confirmed as an independent prognostic factor for LUAD occurrence. The high expression level of FANCD2 was associated with an advantaged TNM stage, a less chemotherapy sensitivity, a low ImmuneScore, which indicated a deactivation status in immune microenvironment, a high tumor mutation burden, and a poor survival for LUAD patients. Pathway enrichment analysis showed that FANCD2 were involved in response to oxidative stress and neutrophil mediated immunity. Quantitative real-time PCR and immunohistochemistry staining showed that the expression level of FANCD2 is higher in LUAD patients than normal tissue samples, which was in accordance with the database report.Conclusion. FANCD2, a key gene related to autophagy-dependent ferroptosis, could work as a biomarker, which predicts the survival, chemotherapy sensitivity, tumor immunity and mutation burden of LUAD. Research of autophagy-dependent ferroptosis and targeting the FANCD2 may offer a new perspective for the treatment and improvement of prognosis in LUAD.

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