Dataset Information

Characterization of gene expression profiles of esophageal cancer patients with different nonsynonymous tumor mutation burden.

ABSTRACT:

Background

Nonsynonymous tumor mutation burden (NSTMB) could affect the prognosis of esophageal cancer (EC) patients, but differentially expressed genes between EC patients with different NSTMB have not been explored. Our study aimed to compare differentially expressed genes between EC patients with different NSTMB (high vs. low).

Methods

RNA-seq data for EC patients were downloaded from The Cancer Genome Atlas (TCGA). The edgeR package was used to identify differentially expressed genes between patients with different NSTMB. Cell type identification by estimating relative subsets of known RNA transcripts (CIBERSORT) software was employed to underscore immune cell differences between patients with different NSTMB.

Results

In total, we discovered 2215 differentially expressed genes between patients with different NSTMB, among which 842 genes were upregulated and 1373 downregulated in patients with high NSTMB. The differentially expressed genes were enriched in pathways such as heme binding and structural molecule activity. We built a logistic model that may be used to predict patients' NSTMB. We found that tumors with high NSTMB had a significantly higher percentage of resting natural killer (NK) cells than those with low NSTMB (P = 0.028). The percentages of regulatory T (Treg) and CD8⁺ T cells were also higher in those with high NSTMB, although it was not statistically significant (P = 0.064 for Treg cells and P = 0.12 for CD8⁺ T cells).

Conclusions

NSTMB may cause changes in gene expression and immune cell infiltration in EC patients, and affect the overall survival of EC patients.

Key points

Significant findings of the study This study found differentially expressed genes and differences in infiltration of immune cells between esophageal cancer (EC) with different NSTMB. What this study adds This study highlights differences between EC patients with different NSTMB.

SUBMITTER: Li J

PROVIDER: S-EPMC7396386 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Publications

Characterization of gene expression profiles of esophageal cancer patients with different nonsynonymous tumor mutation burden.

Li Jiawei J Chen Haiqing H Guo Haifa H Qiu Mantang M Yang Fan F

Thoracic cancer 20200617 8

<h4>Background</h4>Nonsynonymous tumor mutation burden (NSTMB) could affect the prognosis of esophageal cancer (EC) patients, but differentially expressed genes between EC patients with different NSTMB have not been explored. Our study aimed to compare differentially expressed genes between EC patients with different NSTMB (high vs. low).<h4>Methods</h4>RNA-seq data for EC patients were downloaded from The Cancer Genome Atlas (TCGA). The edgeR package was used to identify differentially expresse ...[more]

PMID: 32558329

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Project description:BackgroundImmunotherapy is a vital component in cancer treatment. However, due to the complex genetic bases of cancer, a clear prediction index for efficacy has not been established. Tumor mutation burden (TMB) is one of the essential factors that affect immunotherapeutic efficacies, but it has not been determined whether the mutation is associated with the survival of Skin Cutaneous Melanoma (SKCM) patients. This study aimed at evaluating the correlation between TMB and immune infiltration.MethodsSomatic mutation profiles (n = 467), transcriptome data (n = 471), and their clinical information (n = 447) of all SKCM samples were downloaded from The Cancer Genome Atlas (TCGA) database. For each sample, TMB was calculated as the number of variants per megabase. Based on K-M survival analysis, they were allocated into the high-TMB and low-TMB groups (the optimal cutoff was determined by the 'surv_cutpoint' algorithm of survival R package). Then, Gene ontology (GO) and Gene Set Enrichment Analyses (GSEA) were performed, with immune-associated biological pathways found to be significantly enriched in the low-TMB group. Therefore, immune genes that were differentially expressed between the two groups were evaluated in Cox regression to determine their prognostic values, and a four-gene TMB immune prognostic model (TMB-IP) was constructed.ResultsElevated TMB levels were associated with better survival outcomes in SKCM patients. Based on the cutoff value in OS analysis, they were divided into high-TMB and low-TMB groups. GSEA revealed that the low-TMB group was associated with immunity while intersection analysis revealed that there were 38 differentially expressed immune-related genes between the two groups. Four TMB-associated immune genes were used to construct a TMB-IP model. The AUC of the ROC curve of this model reached a maximum of 0.75 (95%CI, 0.66-0.85) for OS outcomes. Validation in each clinical subgroup confirmed the efficacy of the model to distinguish between high and low TMB-IP score patients.ConclusionsIn SKCM patients, low TMB was associated with worse survival outcomes and enriched immune-associated pathways. The four TMB-associated immune genes model can effectively distinguish between high and low-risk patients.

Project description:ObjectivesVarious genomic alterations and genomic signatures, including ERBB2 amplification, mutations in PIK3CA, AKT1, and ESR1, and tumor mutational burden (TMB), have become important biomarkers for treatment selection in breast cancer (BC). This study aimed to investigate the mutational features of Chinese early-stage BC patients.MethodsTumors and matched blood samples collected from 589 Chinese patients with early-stage BC were sequenced using a commercial gene panel consisting of 520 cancer-related genes to analyze all types of genomic alterations and estimate the TMB status.ResultsA total of 18 genes were found to be more frequently mutated (P<0.05) or amplified (P<0.05) in stage T3-4 tumors as compared with T1-2 tumors. A total of 18 genes were found to be differentially mutated (P<0.05) or amplified (P<0.05) in patients with lymph node metastasis than those without lymph node metastasis. Younger patients (≤35 years) were more frequently identified with mutations or gene amplifications in eleven genes (P<0.05). TMB >10mutations/Mb were found in 5.7% of our cohort. Although the TMB was similar for various molecular subtypes between our cohort and the BC cohort of The Cancer Genome Atlas (TCGA) study, the TMB were statistically different for HR+/HER-, HR+/HER2+, and triple-negative subtypes between our cohort and African Americans in the TCGA study. As compared to the TCGA BC cohort, our cohort had a much earlier median age of diagnosis (48 vs. 58 years, P<0.001), and had significantly lower frequency of triple-negative subtype (11.5% vs. 18.4%, P<0.001) and invasive lobular BC (2.4% vs. 19.0%, P<0.001). Further subgroup analyses revealed that mutation rates in various genes including TP53, ERBB2, and PIK3CA were distinct for patients who were younger (≤35 years), had triple-negative or invasive lobular BC in our cohort than in the TCGA cohort.ConclusionsThis study revealed distinct mutational features of various molecular subtypes of early-stage BC among Chinese patients. Moreover, we provide new insights into the differences in early-stage BC between the East and West.

Dataset Information

Characterization of gene expression profiles of esophageal cancer patients with different nonsynonymous tumor mutation burden.

Background

Methods

Results

Conclusions

Key points

Publications

Characterization of gene expression profiles of esophageal cancer patients with different nonsynonymous tumor mutation burden.

Similar Datasets

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