Identification and Validation of a Prognostic Gene Signature for Diffuse Large B-Cell Lymphoma Based on Tumor Microenvironment-Related Genes

Abstract

Diffuse large B-cell lymphoma (DLBCL) is an extremely heterogeneous tumor entity, which makes prognostic prediction challenging. The tumor microenvironment (TME) has a crucial role in fostering and restraining tumor development. Consequently, we performed a systematic investigation of the TME and genetic factors associated with DLBCL to identify prognostic biomarkers for DLBCL. Data for a total of 1,084 DLBCL patients from the Gene Expression Omnibus database were included in this study, and patients were divided into a training group, an internal validation group, and two external validation groups. We calculated the abundance of immune–stromal components of DLBCL and found that they were related to tumor prognosis and progression. Then, differentially expressed genes were obtained based on immune and stromal scores, and prognostic TME‐related genes were further identified using a protein–protein interaction network and univariate Cox regression analysis. These genes were analyzed by the least absolute shrinkage and selection operator Cox regression model to establish a seven-gene signature, comprising TIMP2, QKI, LCP2, LAMP2, ITGAM, CSF3R, and AAK1. The signature was shown to have critical prognostic value in the training and validation sets and was also confirmed to be an independent prognostic factor. Subgroup analysis also indicated the robust prognostic ability of the signature. A nomogram integrating the seven-gene signature and components of the International Prognostic Index was shown to have value for prognostic prediction. Gene set enrichment analysis between risk groups demonstrated that immune-related pathways were enriched in the low-risk group. In conclusion, a novel and reliable TME relevant gene signature was proposed and shown to be capable of predicting the survival of DLBCL patients at high risk of poor survival.

Prognostication of Primary Tumor Location in Early-Stage Nodal Diffuse Large B-Cell Lymphoma: An Analysis of the SEER Database

“…Few studies have given emphasis on extracellular matrix, an important part of tumor microenvironment. Recently, a group identified a genetic signature based on TME-related genes, comprising TIMP2, QKI, LCP2, LAMP2, ITGAM, CSF3R, and AAK1 [40], by calculating the abundance of immune-stromal components, and from this group they further obtained differentially expressed genes. In our research, we found that extracellular matrix structural constituents such as the networkforming collagen trimer and collagen type IV trimer were upregulated in the Sub-DLBCL group, which may contribute to the development of DLBCL located under diaphragm.…”

Iterated cross validation method for prediction of survival in diffuse large B-cell lymphoma for small size dataset

“…In the similar study published in 2021, Pan et al 49 established a tumor microenvironment (TME) related prognostic signature for DLBCL patients. When combining with IPI components, it is a promising prognostic model not only to help clarifying immune responses in the DLBCL microenvironment but also to indicate new clinical applications for immune therapy and individualized therapy in patients with DLBCL.…”

A Novel Prognostic Model for Patients with Primary Gastric Diffuse Large B-Cell Lymphoma

“…As the data source, SEER, did not provide the IPI scores of the patients, we cannot compare this nomogram with the IPI scoring system. In addition, the results of this study ignored the genetic characteristics, which are now proved to be important in the diagnosis and prognosis of the disease [ 21 , 22 ]. Even so, our study remains an instructive and efficient model of PG-DLBCL prognosis.…”