Chenshen Huang1, Runzhi Huang2,3, Hong Chen4, Zhizhan Ni1, Qi Huang1, Zongqiang Huang2, Bujun Ge1. 1. Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai, China. 2. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. 3. Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China. 4. Center for Difficult and Complicated Abdominal Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
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.
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.
Authors: Darren A Cusanovich; Riza Daza; Andrew Adey; Hannah A Pliner; Lena Christiansen; Kevin L Gunderson; Frank J Steemers; Cole Trapnell; Jay Shendure Journal: Science Date: 2015-05-07 Impact factor: 47.728
Authors: Jason D Buenrostro; Paul G Giresi; Lisa C Zaba; Howard Y Chang; William J Greenleaf Journal: Nat Methods Date: 2013-10-06 Impact factor: 28.547
Authors: Aaron M Newman; Chih Long Liu; Michael R Green; Andrew J Gentles; Weiguo Feng; Yue Xu; Chuong D Hoang; Maximilian Diehn; Ash A Alizadeh Journal: Nat Methods Date: 2015-03-30 Impact factor: 28.547
Authors: Bo Li; Eric Severson; Jean-Christophe Pignon; Haoquan Zhao; Taiwen Li; Jesse Novak; Peng Jiang; Hui Shen; Jon C Aster; Scott Rodig; Sabina Signoretti; Jun S Liu; X Shirley Liu Journal: Genome Biol Date: 2016-08-22 Impact factor: 13.583