Immunogenic Cell Death-related Signature Evaluates the Tumor Microenvironment and Predicts the Prognosis in Diffuse Large B-Cell Lymphoma.

in Biochemical genetics by Shengqiang Huang, Wenbin Liu, Qiuling Zhao, Ting Chen, Ruyi Huang, Liangliang Dong, Zilin Nian, Lin Yang

TLDR

  • The study looked at how a process called Immunogenic Cell Death (ICD) affects diffuse large B-cell lymphoma (DLBCL). They found that a certain group of genes related to ICD were different in DLBCL patients with a poor prognosis. They also found that the immune system in this group was suppressed. The study provides new information about how ICD may be used to develop treatments for DLBCL.

Abstract

Current literatures suggest a growing body of evidence highlighting the pivotal role of Immunogenic Cell Death (ICD) in multiple tumor types. Nevertheless, the potential and mechanisms of ICD in diffuse large B-cell lymphoma (DLBCL) remain inadequately studied. To address this gap, our current study aims to examine the impact of ICD on DLBCL and identify a corresponding gene signature in DLBC. Using the expression profiles of ICD-associated genes, the gene expression omnibus (GEO) samples were segregated into ICD-high and ICD-low subtypes utilizing non-negative matrix factorization clustering. Next, univariate and LASSO Cox regression analyses were employed to establish the ICD-related gene signature. Subsequently, the CIBERSORT tool, ssGSEA, and ESTIMATE algorithm were utilized to examine the association between the signature and tumor immune microenvironment of DLBC. Finally, the oncoPredict algorithm was implemented to evaluate the drug sensitivity prediction of DLBCL patients. These findings suggest that the immune microenvironment of the ICD-high group with a poor prognosis was significantly suppressed. An 8-gene ICD-related signature was identified and validated to prognosticate and evaluate the tumor immune microenvironment in DLBCL. Similarly, the high-risk group exhibited a worse prognosis compared to the low-risk group, and the immune function was considerably suppressed. Moreover, the results of oncoPredict algorithm indicated that patients in the high-risk group exhibited higher sensitivity to Cisplatin, Cytarabine, Epirubicin, Oxaliplatin, and Vincristine with low IC50. In conclusion, the present study provides novel insights into the role of ICD in DLBCL by identifying a new biomarker for the disease and may have implications for the development of immune-targeted therapies for the tumor.

Overview

  • The study aims to examine the impact of Immunogenic Cell Death (ICD) on diffuse large B-cell lymphoma (DLBCL) and identify a corresponding gene signature in DLBC. The study uses the expression profiles of ICD-associated genes, the gene expression omnibus (GEO) samples were segregated into ICD-high and ICD-low subtypes utilizing non-negative matrix factorization clustering. Univariate and LASSO Cox regression analyses were employed to establish the ICD-related gene signature. The CIBERSORT tool, ssGSEA, and ESTIMATE algorithm were utilized to examine the association between the signature and tumor immune microenvironment of DLBC. Finally, the oncoPredict algorithm was implemented to evaluate the drug sensitivity prediction of DLBCL patients.

Comparative Analysis & Findings

  • The study identifies an 8-gene ICD-related signature that prognosticates and evaluates the tumor immune microenvironment in DLBCL. The immune microenvironment of the ICD-high group with a poor prognosis was significantly suppressed. The high-risk group exhibited a worse prognosis compared to the low-risk group, and the immune function was considerably suppressed. Moreover, the results of oncoPredict algorithm indicated that patients in the high-risk group exhibited higher sensitivity to Cisplatin, Cytarabine, Epirubicin, Oxaliplatin, and Vincristine with low IC50.

Implications and Future Directions

  • The study provides novel insights into the role of ICD in DLBCL by identifying a new biomarker for the disease and may have implications for the development of immune-targeted therapies for the tumor. Future research directions could include validating the ICD-related gene signature in a larger cohort of DLBCL patients, exploring the mechanisms underlying the immune suppression in the ICD-high group, and investigating the potential of immune-targeted therapies in DLBCL.
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