Published online Jun 26, 2021. doi: 10.12998/wjcc.v9.i18.4585
Peer-review started: November 16, 2020
First decision: January 17, 2021
Revised: January 26, 2021
Accepted: February 24, 2021
Article in press: February 24, 2021
Published online: June 26, 2021
Processing time: 207 Days and 1.9 Hours
Diffuse large B-cell lymphoma (DLBCL) is a lymphoma with high mortality rates. Even though some therapeutic strategies are applied in clinical practice, the prognoses of DLBCL patients remain unsatisfactory. Therefore, the screening of novel therapeutic targets or prognostic biomarkers could be an important work for DLBCL therapy, which could contribute to the improvement of treatment regimens.
This study aimed to identify the novel biomarkers of DLBCL, and analyze the prognostic value of these biomarkers.
This study addressed the question of the novel biomarkers and potential mechanism involved in the development of DLBCL.
The differentially expressed genes (DEGs) of DLBCL were examined with the GSE60 dataset, and these DEGs were applied to the STRING tool to conduct protein-protein interaction (PPI) analysis. The key hub genes based on PPI analysis were then applied to the GEPIA portal to analyze the expression level in DLBCL. The gene alteration level and the correlation between fibronectin protein level and secreted protein acidic and cysteine-rich messenger ribonucleic acid expression was analyzed in cBioportal. Moreover, the expression level of the hub genes in different stages were investigated in the UALCAN portal. The gene correlation analysis was conducted in GEPIA. The TIMER portal was used to evaluate the correlation between the gene expression and tumor purity, infiltrated stromal cells and infiltrated level of cancer-associated fibroblasts.
The top 20 DEGs in DLBCL were obtained, and the hub genes (A2M, CTSB, FN1, MMP9, and SPARC) were identified based on DEGs through PPI analysis. The five hub genes were overexpressed in DLBCL, and gene alteration was also confirmed in cBioportal, including messenger ribonucleic acid high amplification and missense mutation. Furthermore, the five hub genes had a positive correlation with the tumor stage. Besides, the positive correlation between the five hub genes levels and the tumor purity was also confirmed by the overexpression of the five hub genes in DLBCL. More interestingly, there was a significant correlation between the five hub genes’ expression level and the stromal infiltration score, especially in the correlation analysis with cancer-associated fibroblasts’ infiltration level.
A five hub gene signatures were identified in DLBCL, and the overexpression of these five genes were closely associated with the progression of DLBCL. The mechanism evaluation showed positive correlation between the five genes’ expression levels and infiltrated levels of stromal cells, especially for the cancer-associated fibroblasts. In summary, the five gene signatures have potential values as novel therapeutic targets or biomarkers for DLBCL.
In this project, we identified five gene signatures in DLBCL and that the overexpression of the five genes is closely associated with the disease development, suggesting that the five gene signatures might be novel therapeutic targets for DLBCL, especially in the regulation of cancer-associated fibroblasts. In our subsequent work, the detailed mechanism underlying the regulation of the five genes in the tumor microenvironment will be addressed, which could promote the further understanding of these five gene signatures in DLBCL.