Expression of N6-methyladenosine (m6A) regulators correlates with immune microenvironment characteristics and predicts prognosis in diffuse large cell lymphoma (DLBCL)
| Autor: | Haoyuan Hong, Zhigang Peng, Meiwei Li, Zucheng Xie, Zhendong He, Qingyuan Xu |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adenosine
medicine.medical_treatment immune microenvironment Regulator BTLA m6A regulator Bioengineering Biology Applied Microbiology and Biotechnology Immune system TIGIT Biomarkers Tumor Tumor Microenvironment medicine Humans Clinical significance prognostic signature General Medicine Immunotherapy Prognosis Immune checkpoint Gene Expression Regulation Neoplastic DLBCL Cancer research Lymphoma Large B-Cell Diffuse KIR3DL1 TP248.13-248.65 Research Article Research Paper Biotechnology |
| Zdroj: | Bioengineered article-version (VoR) Version of Record Bioengineered, Vol 12, Iss 1, Pp 6115-6133 (2021) |
| ISSN: | 2165-5987 2165-5979 |
| DOI: | 10.1080/21655979.2021.1972644 |
| Popis: | This study conducted a comprehensive analysis of the clinical significance of N6-methyladenosine (m6A) regulators and their relationship with immune microenvironment characteristics in diffuse large cell lymphoma (DLBCL). Consensus clustering was performed to molecularly discriminate DLBCL subtypesbased on m6A regulators’ expression. Using the Cox and Lasso regression algorithm, survival-associated m6A regulators were identified, and a m6A-based prognostic signature was established. The influence of m6A risk on immune cell infiltration, immune checkpoint genes, cancer immunity cycle, and immunotherapeutic response was evaluated. Potential molecular pathways related to m6A risk were investigated using gene set enrichment analysis. The m6A regulators showed satisfactory performance in distinguishing DLBCL subgroups with distinct clinical traits and outcomes. A six m6A regulator-based prognostic signature was established and validated as an independent predictor, which separated patients into low- and high-risk groups. High-risk m6A indicated worse survival. The B cells naïve, T cells gamma delta, and NK cells resting were the three most affected immune cells by m6A risk. Up-regulated (PDCD1 and KIR3DL1) and down-regulated (TIGIT, IDO1, and BTLA) immune checkpoint genes in the high-risk group were identified. The m6A risk was found to influence several steps in the cancer immunity cycle. Patients with high-risk m6A were more likely to benefit from immunotherapy. Biological function enrichment analysis revealed that high-risk m6A to be tended related to malignant tumor characteristics, while low-risk m6A showed trend to be related to defensive response processes. Collectively, the m6A-based prognostic signature could be a practical prognostic predictor for DLBCL and immune microenvironment characteristics affected by m6A may be part of the mechanism. |
| Databáze: | OpenAIRE |
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