Retrospective Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jun 26, 2021; 9(18): 4585-4598
Published online Jun 26, 2021. doi: 10.12998/wjcc.v9.i18.4585
Evaluation of a five-gene signature associated with stromal infiltration for diffuse large B-cell lymphoma
Ying-Yu Nan, Wen-Jun Zhang, De-Hong Huang, Qi-Ying Li, Yang Shi, Tao Yang, Xi-Ping Liang, Chun-Yan Xiao, Bing-Ling Guo, Ying Xiang
Ying-Yu Nan, Wen-Jun Zhang, De-Hong Huang, Qi-Ying Li, Yang Shi, Tao Yang, Xi-Ping Liang, Chun-Yan Xiao, Bing-Ling Guo, Ying Xiang, Department of Hematology, Chongqing University Cancer Hospital, Chongqing 400030, China
Author contributions: Xiang Y conceived and designed the study; Nan YY, Zhang WJ and Huang DH conducted the experiments, data analysis and manuscript drafting, and the three authors contributed equally to the study; Yang T performed the statistical analyses; Li QY, Shi Y, Liang XP, Xiao CY and Guo BL participated intellectual discussions and revised the manuscript; All authors reviewed and approved the final manuscript.
Supported by the Natural Science Foundation of Chongqing, No. cstc2019jcyj-msxmX0793.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Chongqing University Cancer Hospital.
Informed consent statement: The patients were not required to give informed consent to participate in this study because the analysis used anonymous data obtained from an archival database.
Conflict-of-interest statement: All authors declare having no conflict of interests.
Data sharing statement: The supporting information is provided along with the BPG online publication, and no additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Ying Xiang, MD, MSc, Chief Doctor, Department of Hematology, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing 400030, China. xiangying0331@163.com
Received: November 16, 2020
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
ARTICLE HIGHLIGHTS
Research background

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.

Research motivation

This study aimed to identify the novel biomarkers of DLBCL, and analyze the prognostic value of these biomarkers.

Research objectives

This study addressed the question of the novel biomarkers and potential mechanism involved in the development of DLBCL.

Research methods

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.

Research results

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.

Research conclusions

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.

Research perspectives

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.