M6A-mediated Molecular Patterns and Tumor Microenvironment Infiltration Characterization in Nasopharyngeal Carcinoma

Overview

Journal Cancer Biol Ther

Specialties Oncology
Pharmacology

Date 2024 Mar 27

PMID 38532632

Authors

Yong Wang

Lisha Peng

Feng Wang

Affiliations

Soon will be listed here.

Abstract

N6-methyladenosine (m6A) is the most predominant RNA epigenetic regulation in eukaryotic cells. Numerous evidence revealed that m6A modification exerts a crucial role in the regulation of tumor microenvironment (TME) cell infiltration in several tumors. Nevertheless, the potential role and mechanism of m6A modification in nasopharyngeal carcinoma (NPC) remains unknown. mRNA expression data and clinical information from GSE102349, and GSE53819 datasets obtained from Gene Expression Omnibus (GEO) was used for differential gene expression and subsequent analysis. Consensus clustering was used to identify m6A-related molecular patterns of 88 NPC samples based on prognostic m6A regulators using Univariate Cox analysis. The TME cell-infiltrating characteristics of each m6A-related subclass were explored using single-sample gene set enrichment (ssGSEA) algorithm and CIBERSORT algotithm. DEGs between two m6A-related subclasses were screened using edgeR package. The prognostic signature and predicated nomogram were constructed based on the m6A-related DEGs. The cell infiltration and expression of prognostic signature in NPC was determined using immunohistochemistry (IHC) analysis. Chi-square test was used to analysis the significance of difference of the categorical variables. And survival analysis was performed using Kaplan-Meier plots and log-rank tests. The NPC samples were divided into two m6A-related subclasses. The TME cell-infiltrating characteristics analyses indicated that cluster 1 is characterized by immune-related and metabolism pathways activation, better response to anit-PD1 and anti-CTLA4 treatment and chemotherapy. And cluster 2 is characterized by stromal activation, low expression of HLA family and immune checkpoints, and a worse response to anti-PD1 and anti-CTLA4 treatment and chemotherapy. Furthermore, we identified 1558 DEGs between two m6A-related subclasses and constructed prognostic signatures to predicate the progression-free survival (PFS) for NPC patients. Compared to non-tumor samples, REEP2, TMSB15A, DSEL, and ID4 were upregulated in NPC samples. High expression of REEP2 and TMSB15A showed poor survival in NPC patients. The interaction between REEP2, TMSB15A, DSEL, ID4, and m6A regulators was detected. Our finding indicated that m6A modification plays an important role in the regulation of TME heterogeneity and complexity.

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References

Le P, Keysar S, Miller B, Eagles J, Chimed T, Reisinger J . Wnt signaling dynamics in head and neck squamous cell cancer tumor-stroma interactions. Mol Carcinog. 2018; 58(3):398-410. PMC: 6460915. DOI: 10.1002/mc.22937. View

Zhang Y, Chen L, Hu G, Zhang N, Zhu X, Yang K . Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med. 2019; 381(12):1124-1135. DOI: 10.1056/NEJMoa1905287. View

Yang Y, Hsu P, Chen Y, Yang Y . Dynamic transcriptomic mA decoration: writers, erasers, readers and functions in RNA metabolism. Cell Res. 2018; 28(6):616-624. PMC: 5993786. DOI: 10.1038/s41422-018-0040-8. View

Fiala G, Minguet S . Caveolin-1: The Unnoticed Player in TCR and BCR Signaling. Adv Immunol. 2018; 137:83-133. DOI: 10.1016/bs.ai.2017.12.002. View

Hoshida Y, Brunet J, Tamayo P, Golub T, Mesirov J . Subclass mapping: identifying common subtypes in independent disease data sets. PLoS One. 2007; 2(11):e1195. PMC: 2065909. DOI: 10.1371/journal.pone.0001195. View

Lu H, Li Z, Ding M, Liang C, Weng X, Sheng Y . Trametinib enhances ATRA-induced differentiation in AML cells. Leuk Lymphoma. 2021; 62(14):3361-3372. DOI: 10.1080/10428194.2021.1961231. View

Netea M, Joosten L, Latz E, Mills K, Natoli G, Stunnenberg H . Trained immunity: A program of innate immune memory in health and disease. Science. 2016; 352(6284):aaf1098. PMC: 5087274. DOI: 10.1126/science.aaf1098. View

Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

Zhang P, He Q, Lei Y, Li Y, Wen X, Hong M . mA-mediated ZNF750 repression facilitates nasopharyngeal carcinoma progression. Cell Death Dis. 2018; 9(12):1169. PMC: 6281568. DOI: 10.1038/s41419-018-1224-3. View

10.

Hinshaw D, Shevde L . The Tumor Microenvironment Innately Modulates Cancer Progression. Cancer Res. 2019; 79(18):4557-4566. PMC: 6744958. DOI: 10.1158/0008-5472.CAN-18-3962. View

11.

Courtney A, Lo W, Weiss A . TCR Signaling: Mechanisms of Initiation and Propagation. Trends Biochem Sci. 2017; 43(2):108-123. PMC: 5801066. DOI: 10.1016/j.tibs.2017.11.008. View

12.

Campion N, Ally M, Jank B, Ahmed J, Alusi G . The molecular march of primary and recurrent nasopharyngeal carcinoma. Oncogene. 2021; 40(10):1757-1774. DOI: 10.1038/s41388-020-01631-2. View

13.

Zhang L, MacIsaac K, Zhou T, Huang P, Xin C, Dobson J . Genomic Analysis of Nasopharyngeal Carcinoma Reveals TME-Based Subtypes. Mol Cancer Res. 2017; 15(12):1722-1732. DOI: 10.1158/1541-7786.MCR-17-0134. View

14.

Wang Y, Zhang S, Li H, Wang H, Zhang T, Hutchinson M . Small-Molecule Modulators of Toll-like Receptors. Acc Chem Res. 2020; 53(5):1046-1055. DOI: 10.1021/acs.accounts.9b00631. View

15.

Li M, Zha X, Wang S . The role of N6-methyladenosine mRNA in the tumor microenvironment. Biochim Biophys Acta Rev Cancer. 2021; 1875(2):188522. DOI: 10.1016/j.bbcan.2021.188522. View

16.

Burger J, Wiestner A . Targeting B cell receptor signalling in cancer: preclinical and clinical advances. Nat Rev Cancer. 2018; 18(3):148-167. DOI: 10.1038/nrc.2017.121. View

17.

Meyer K, Jaffrey S . The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol. 2014; 15(5):313-26. PMC: 4393108. DOI: 10.1038/nrm3785. View

18.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

19.

Lam W, Chan J . Recent advances in the management of nasopharyngeal carcinoma. F1000Res. 2018; 7. PMC: 6249636. DOI: 10.12688/f1000research.15066.1. View

20.

Chen Y, Chan A, Le Q, Blanchard P, Sun Y, Ma J . Nasopharyngeal carcinoma. Lancet. 2019; 394(10192):64-80. DOI: 10.1016/S0140-6736(19)30956-0. View