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14 January 2022 : Database Analysis  

H2A Histone Family Member Z (H2AFZ) Serves as a Prognostic Biomarker in Lung Adenocarcinoma: Bioinformatic Analysis and Experimental Validation

Zongkuo Li12AE, Menglong Hu12A, Jinhuan Qiu12C, Junkai Feng12C, Ruizhen Zhang1C, Huifang Wu1D, Guiming Hu1D, Jingli Ren1G*

DOI: 10.12659/MSM.933447

Med Sci Monit 2022; 28:e933447

Abstract

BACKGROUND: H2A histone family member Z (H2AFZ) is a special subtype in the H2A histone family, which participates in the regulation of gene transcription. Nevertheless, little is known about the role of H2AFZ in the tumor microenvironment and genetic factors associated with lung cancer.

MATERIAL AND METHODS: The expression of H2AFZ in LUAD was analyzed via Tumor Immune Estimation Resource (TIMER), the Cancer Genome Atlas (TCGA), and Gene Expression Omnibus (GEO) databases at the mRNA level. To detect the protein expression level of H2AFZ, immunohistochemistry (IHC) was performed using LUAD tissues and non-tumor lung tissues. Kaplan-Meier survival analysis and Cox regression analysis were conducted to identify the effect of H2AFZ expression on overall survival (OS) based on TCGA-LUAD and the GEO dataset GSE68465 cohorts, and our LUAD patient cohort was used for validation. Identification of signaling pathways associated with the expression of H2AFZ was performed using Gene Set Enrichment Analysis (GSEA). The influences of expression of H2AFZ on tumor immune-infiltrating cell (TIICs) were assessed via TIMER and CIBERSORT.

RESULTS: The expression of H2AFZ was increased in LUAD tissues at both mRNA and protein levels. In addition, high expression of H2AFZ predicted poor OS and might be an independent prognostic predictor in LUAD patients. Moreover, H2AFZ affected the relative proportion of TIICs and was positively associated with Myeloid-derived suppressor cells (MDSC) infiltration level in LUAD.

CONCLUSIONS: H2AFZ was upregulated in LUAD and related to poor prognosis of LUAD patients; thus, it could be an underlying prognostic biomarker correlated with immune infiltration in LUAD.

Keywords: Adenocarcinoma of Lung, biomarkers, H2A.Z Protein, Arabidopsis

Comments

Figures

Figure 1. H2AFZ expression in LUAD tissue at the mRNA level. (A) Differential expression of H2AFZ in different cancer tissues compared with normal tissues in the Timer 2.0 database (* p<0.05, ** p<0.01, *** p<0.001). (B–D) Comparisons of H2AFZ expression levels between LUAD tissues and normal lung tissues in different datasets including TCGA, GSE10072 and GSE43458 datasets. R 4.1.0 software, (R Development Core Team, Vienna).Figure 2. Immunohistochemistry of H2AFZ in the LUAD tissues and normal lung tissues. (A) Nuclear staining in LUAD tissues (left panel: 20×, right panel: 40×). (B) Cells in adjacent normal tissues are not stained (left panel: 20×, right panel: 40×). (C) Differential expression of H2AFZ protein in LUAD tissues and normal lung tissues. GraphPad Prism 7.0 software (GraphPad Software Inc., La Jolla, CA, USA).Figure 3. Gene enrichment analysis of H2AFZ co-expressed genes based on the TCGA-LUAD data. (A) Heatmaps showing genes positively and negatively correlated with H2AFZ in LUAD (top50). (B, C) Enriched GO terms and enriched KEGG pathways of H2AFZ-associated genes. R 4.1.0 software, (R Development Core Team, Vienna).Figure 4. The expression level of H2AFZ in subgroups of patients with LUAD. (A–C) The expression of H2AFZ is grouped by pathological stage, T, and N classification based on TCGA-LUAD data. (D) Differential mRNA expression of H2AFZ in LUAD with different T classifications in GSE68465. R 4.1.0 software (R Development Core Team, Vienna).Figure 5. Kaplan-Meier survival curves comparing the high and low expression of H2AFZ in TCGA-LUAD, GSE68465, and our cohorts. (A) Kaplan-Meier (KM) survival analysis of H2AFZ in LUAD based on the TCGA-LUAD cohort. (B) Kaplan-Meier (KM) survival analysis of H2AFZ in LUAD based on the GSE68465. (C) Kaplan-Meier (KM) survival analysis of H2AFZ in LUAD based on our cohort. GraphPad Prism 7.0 software (GraphPad Software Inc., La Jolla, CA, USA).Figure 6. Forest plot for the multivariate Cox proportional hazard regression model in 2 datasets. (A) TCGA-LUAD cohort. (B) GSE68465. HR – hazard ratio; CI – confidence interval. * p<0.05, ** p<0.01, *** p<0.001. R 4.1.0 software, (R Development Core Team, Vienna).Figure 7. The significantly enriched signaling pathways in the high-expression phenotypes of H2AFZ in LUAD. GSEA 3.0 software (Massachusetts Institute of Technology, Cambridge, MA, USA).Figure 8. Correlation of H2AFZ with TIICs in LUAD. (A) Proportions of the 22 tumor-infiltrating immune cell subtypes in high and low H2AFZ expression groups. (B) Correlation between H2AFZ expression and immune cells in LUAD. (C) The combined impact of H2AFZ expression and MDSC infiltration on the survival of LUAD patients. R 4.1.0 software (R Development Core Team, Vienna).

Editorial

01 January 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

SARS-CoV-2/COVID-19

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Med Sci Monit In Press; DOI: 10.12659/MSM.935474  

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In Press

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Med Sci Monit In Press; DOI: 10.12659/MSM.936131  

27 Jan 2022 : Clinical Research  

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Med Sci Monit In Press; DOI: 10.12659/MSM.935002  

25 Jan 2022 : Editorial  

Editorial: The 2022 World Health Organization (WHO) Priority Recommendations and Response to the Omicron Va...

Med Sci Monit In Press; DOI: 10.12659/MSM.936199  

25 Jan 2022 : Clinical Research  

Experience of the Polish Medical Air Rescue Service During the First Year of the COVID-19 Pandemic and Meas...

Med Sci Monit In Press; DOI: 10.12659/MSM.935474  

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750