Dataset Information

Chromatin Accessibility Regulates Gene Expression and Correlates With Tumor-Infiltrating Immune Cells in Gastric Adenocarcinoma.

ABSTRACT:

Background

We explored key molecules affecting the prognosis of gastric adenocarcinoma (STAD) using co-analysis of chromatin accessibility (ATAC-seq), mRNA expression (RNA-seq), and overall survival.

Methods

We used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles to identify genes with chromatin accessibilities in their promoter regions. The RNA-seq profiles were processed for differentially expressed genes (DEGs) at mRNA level. The DEGs with chromatin accessibilities in promoter regions were further filtered using the Pearson correlation with TP53 expression. After co-analysis, genes were identified for the prognostic value using Kaplan-Meier method, followed by Pearson correlation analysis with significant pathways. For verification, we acquired clinical samples for qPCR and immunohistochemistry (IHC). Multidimensional database validations were performed to prevent the bias introduced by the use of a single database.

Results

We identified 11,557 DEGs and 57 genes with chromatin accessibilities. The co-analysis of ATAC-seq, RNA-seq, and clinical survival data revealed that interleukin-18 binding protein (IL18BP), with significant chromatin accessibility in its promoter region and differential mRNA expression, might be directly regulated by TP53 and influence STAD prognosis. Further, gene set variation analysis indicated that IL18BP may impact the survival of STAD patients in an immune-related manner. According to the CIBERSORT algorithm and Pearson correlation, the integration of IL18BP and CD4+ T memory cells may play an important role in the prognosis of STAD patients.

Conclusion

IL18BP, regulated by TP53, may serve as a key molecule affecting STAD prognosis. And the mechanism is proposed to be the interaction between IL18BP and CD4+ T cells.

SUBMITTER: Huang C

PROVIDER: S-EPMC7813815 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Chromatin Accessibility Regulates Gene Expression and Correlates With Tumor-Infiltrating Immune Cells in Gastric Adenocarcinoma.

Huang Chenshen C Huang Runzhi R Chen Hong H Ni Zhizhan Z Huang Qi Q Huang Zongqiang Z Ge Bujun B

Frontiers in oncology 20210105

<h4>Background</h4>We explored key molecules affecting the prognosis of gastric adenocarcinoma (STAD) using co-analysis of chromatin accessibility (ATAC-seq), mRNA expression (RNA-seq), and overall survival.<h4>Methods</h4>We used the assay for transposase-accessible chromatin using sequencing (ATAC-seq) profiles to identify genes with chromatin accessibilities in their promoter regions. The RNA-seq profiles were processed for differentially expressed genes (DEGs) at mRNA level. The DEGs with ch ...[more]

PMID: 33469515

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Project description:BackgroundApolipoprotein B mRNA editing enzyme catalytic polypeptide-like 2 (APOBEC2) is associated with nucleotide alterations in the transcripts of tumor-related genes which are contributed to carcinogenesis. Expression and prognosis value of APOBEC2 in stomach adenocarcinoma (STAD) remains unclear.MethodsThe APOBEC2 gene alteration frequency of STAD and APOBEC2 gene expression in STAD and normal tissues were investigated in cBioportal and GEPIA, respectively. We detected expression of APOBEC2, infiltration of CD66b+ tumor-associated neutrophils and CD163+ tumor-associated macrophages in tissue microarrays by immunohistochemistry. APOBEC2 gene expression was explored by western blot and qRT-PCR. Relationships between APOBEC2 and CD66b, CD163, and other clinicopathological characteristics were investigated. Associations among APOBEC2 expression status and patient survival outcome were further analyzed.ResultsAPOBEC2 gene alteration frequency was 5%, and APOBEC2 gene was downexpressed in STAD compared to normal tissues (P < 0.05). APOBEC2 expression status were associated with the infiltration of CD66b+ TANs, differentiation grade, TNM stage, histological type and gender (all P < 0.05) in STAD. Little or no APOBEC2 expression was detected in STAD and adjacent normal tissues by western blot. We failed to show that APOBEC2 was an independent risk factor for OS (Hazard Ratio 0.816, 95%CI 0.574-1.161, P = 0.259) or DFS (Hazard Ratio 0.821, 95%CI 0.578-1.166, P = 0.270) in STAD by multivariate Cox regression analysis, but APOBEC2 negative subgroup has a worse OS and DFS among patients with adjuvant chemotherapy.ConclusionsAPOBEC2 correlates with CD66b, differentiation grade, TNM stages, histological classification, and gender in STAD. APOBEC2 is not an independent prognostic factor for STAD, our results suggest that patients with positive APOBEC2 can benefit from postoperative chemotherapy, and combination of APOBEC2 and CD66b is helpful to further stratify patients into different groups with distinct prognoses.

Project description:BackgroundGastric cancer (GC) is the fourth most frequently diagnosed malignancy and the second leading cause of cancer-associated mortality worldwide. The tumor microenvironment, especially tumor-infiltrating immune cells (TIICs), exhibits crucial roles both in promoting and inhibiting cancer growth. The aim of the present study was to evaluate the landscape of TIICs and develop a prognostic nomogram in GC.Materials and methodsA gene expression profile obtained from a dataset from The Cancer Genome Atlas (TCGA) was used to quantify the proportion of 22 TIICs in GC by the CIBERSORT algorithm. LASSO regression analysis and multivariate Cox regression were applied to select the best survival-related TIICs and develop an immunoscore formula. Based on the immunoscore and clinical information, a prognostic nomogram was built, and the predictive accuracy of it was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC) and the calibration plot. Furthermore, the nomogram was validated by data from the International Cancer Genome Consortium (ICGC) dataset.ResultsIn the GC samples, macrophages (25.3%), resting memory CD4 T cells (16.2%) and CD8 T cells (9.7%) were the most abundant among 22 TIICs. Seven TIICs were filtered out and used to develop an immunoscore formula. The AUC of the prognostic nomogram in the TCGA set was 0.772, similar to that in the ICGC set (0.730) and whole set (0.748), and significantly superior to that of TNM staging alone (0.591). The calibration plot demonstrated an outstanding consistency between the prediction and actual observation. Survival analysis revealed that patients with GC in the high-immunoscore group exhibited a poor clinical outcome. The result of multivariate analysis revealed that the immunoscore was an independent prognostic factor.DiscussionThe immunoscore could be used to reinforce the clinical outcome prediction ability of the TNM staging system and provide a convenient tool for risk assessment and treatment selection for patients with GC.

Dataset Information

Chromatin Accessibility Regulates Gene Expression and Correlates With Tumor-Infiltrating Immune Cells in Gastric Adenocarcinoma.

Background

Methods

Results

Conclusion

Publications

Chromatin Accessibility Regulates Gene Expression and Correlates With Tumor-Infiltrating Immune Cells in Gastric Adenocarcinoma.

Similar Datasets

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