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
Affiliations
Cheng Xing
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Shicong Zhu
Department of Geriatrics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Wenzhe Yan
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Hongkai zhu
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Zineng Huang
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Yan Zhao
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Wancheng Guo
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Huifang Zhang
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Le Yin
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Xueqin Ruan
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Zeyue Deng
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Peilong Wang
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Zhao Cheng
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China
Zhihua Wang
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China; Corresponding author. Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hongling Peng
Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China; Institute of Molecular Hematology, Central South University, Changsha, Hunan, China; Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies, Changsha, Hunan, China; Hunan Key Laboratory of Tumor Models and Individualized Medicine, Changsha, Hunan, China; Corresponding author. Department of Hematology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
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.
