Identification and validation of 5-methylcytosine-associated genes in diffuse large B-cell lymphoma

Cheng Xing; Shicong Zhu; Wenzhe Yan; Hongkai Zhu; Zineng Huang; Yan Zhao; Wancheng Guo; Huifang Zhang; Le Yin; Xueqin Ruan; Zeyue Deng; Peilong Wang; Zhao Cheng; Zhihua Wang; Hongling Peng

doi:10.1016/j.heliyon.2023.e22209

Identification and validation of 5-methylcytosine-associated genes in diffuse large B-cell lymphoma

Heliyon. 2023 Nov 10;9(11):e22209. doi: 10.1016/j.heliyon.2023.e22209. eCollection 2023 Nov.

Authors

Cheng Xing^{1

2

3}, Shicong Zhu⁴, Wenzhe Yan^{1

2

3}, Hongkai Zhu^{1

2

3}, Zineng Huang^{1

2

3}, Yan Zhao^{1

2

3}, Wancheng Guo^{1

2

3}, Huifang Zhang^{1

2

3}, Le Yin^{1

2

3}, Xueqin Ruan^{1

2

3}, Zeyue Deng^{1

2

3}, Peilong Wang^{1

2

3}, Zhao Cheng^{1

2

3}, Zhihua Wang^{1

2

3}, Hongling Peng^{1

2

3

5}

Affiliations

¹ Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Institute of Molecular Hematology, Central South University, Changsha, Hunan, China.
³ Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China.
⁴ Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁵ Hunan Key Laboratory of Tumor Models and Individualized Medicine, Changsha, Hunan, China.

Abstract

5-methylcytosine modifications play a significant role in carcinogenesis; however, studies exploring 5-methylcytosine-related genes in diffuse large B-cell lymphoma patients are lacking. In this study, we aimed to understand the potential role and clinical prognostic impact of 5-methylcytosine regulators in diffuse large B-cell lymphoma and identify a prognostic biomarker based on 5-methylcytosine-associated genes. Gene expression profiles and corresponding clinical information of diffuse large B-cell lymphoma patients and normal controls were obtained from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression databases. Diffuse large B-cell lymphoma was divided into three clusters according to the 5-methylcytosine regulators, and differentially expressed genes were screened among the three clusters. Univariate Cox and Lasso-Cox regression analyses were used to screen prognostic genes and construct a prognostic risk model. Kaplan-Meier curve analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operator characteristic curve analysis were used to evaluate prognostic factors. GSVA was used to enrich potential pathways associated with 5-methylcytosine modification patterns. SsGSEA and CIBERSORT were used to assess immune cell infiltration. Six 5-methylcytosine-related genes (TUBB4A, CD3E, ZNF681, HAP1, IL22RA2, and POSTN) were used to construct a prognostic risk model, which was proved to have a good predictive effect. In addition, univariate and multivariate Cox regression risk scores were independent prognostic factors for diffuse large B-cell lymphoma. Further analysis showed that the 5-methylcytosine risk score was significantly correlated with immune cell infiltration and immune checkpoint of diffuse large B-cell lymphoma. Our study reveals for the first time a potential role for 5-methylcytosine modifications in diffuse large B-cell lymphoma, provides novel insights for future studies on diffuse large B-cell lymphoma, and offers potential prognostic biomarkers and therapeutic targets for patients with diffuse large B-cell lymphoma.

Keywords: 5-Methylcytosine; Biomarker; Diffuse large B-Cell lymphoma; Prognosis; Risk model.