DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas

Naiade Calanca; Ana Lucia Noronha Francisco; Daniela Bizinelli; Hellen Kuasne; Mateus Camargo Barros Filho; Bianca Campos Troncarelli Flores; Clóvis Antonio Lopes Pinto; Claudia Aparecida Rainho; Milena Botelho Pereira Soares; Fabio Albuquerque Marchi; Luiz Paulo Kowalski; Silvia Regina Rogatto

doi:10.1016/j.biopha.2023.115559

DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas

Naiade Calanca, Ana Lucia Noronha Francisco, Daniela Bizinelli, Hellen Kuasne, Mateus Camargo Barros Filho, Bianca Campos Troncarelli Flores, Clóvis Antonio Lopes Pinto, Claudia Aparecida Rainho, Milena Botelho Pereira Soares, Fabio Albuquerque Marchi, Luiz Paulo Kowalski, Silvia Regina Rogatto^*

^*Kontaktforfatter

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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Abstract

Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.

Originalsprog	Engelsk
Artikelnummer	115559
Tidsskrift	Biomedicine & Pharmacotherapy
Vol/bind	167
Antal sider	14
ISSN	0753-3322
DOI	https://doi.org/10.1016/j.biopha.2023.115559
Status	Udgivet - nov. 2023

Bibliografisk note

Funding Information:
This work was supported by grants from Region of Southern Denmark Research Fund, National Institute of Science and Technology in Oncogenomics ( INCITO - Fundação de Amparo à Pesquisa do Estado de São Paulo - FAPESP 2008/57887–9 and Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq 573589/08–9 ). NC was granted with scholarship from the Brazilian Federal Agency for Support and Evaluation of Graduate Education ( CAPES ), within the scope of the Program CAPES-PrInt (process number 88887.310463/2018-00 , mobility number 88887.570391/2020-00).

Publisher Copyright:
© 2023 The Authors

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10.1016/j.biopha.2023.115559Licens: CC BY-NC-ND

Open Access VersionForlagets udgivne version, 9,04 MBLicens: CC BY-NC-ND

SDU link

Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

Citationsformater

Calanca, N., Francisco, A. L. N., Bizinelli, D., Kuasne, H., Barros Filho, M. C., Flores, B. C. T., Pinto, C. A. L., Rainho, C. A., Soares, M. B. P., Marchi, F. A., Kowalski, L. P., & Rogatto, S. R. (2023). DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas. Biomedicine & Pharmacotherapy, 167, Artikel 115559. https://doi.org/10.1016/j.biopha.2023.115559

@article{7f4f78c8698f427e84c665b440cb080a,

title = "DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas",

abstract = "Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.",

keywords = "Deconvolution, DNA methylation, LncRNAs, Oral cancer, Tumor immune microenvironment",

author = "Naiade Calanca and Francisco, {Ana Lucia Noronha} and Daniela Bizinelli and Hellen Kuasne and {Barros Filho}, {Mateus Camargo} and Flores, {Bianca Campos Troncarelli} and Pinto, {Cl{\'o}vis Antonio Lopes} and Rainho, {Claudia Aparecida} and Soares, {Milena Botelho Pereira} and Marchi, {Fabio Albuquerque} and Kowalski, {Luiz Paulo} and Rogatto, {Silvia Regina}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = nov,

doi = "10.1016/j.biopha.2023.115559",

language = "English",

volume = "167",

journal = "Biomedicine & Pharmacotherapy",

issn = "0753-3322",

publisher = "Elsevier Masson",

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Calanca, N, Francisco, ALN, Bizinelli, D, Kuasne, H, Barros Filho, MC, Flores, BCT, Pinto, CAL, Rainho, CA, Soares, MBP, Marchi, FA, Kowalski, LP & Rogatto, SR 2023, 'DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas', Biomedicine & Pharmacotherapy, bind 167, 115559. https://doi.org/10.1016/j.biopha.2023.115559

TY - JOUR

T1 - DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas

AU - Calanca, Naiade

AU - Francisco, Ana Lucia Noronha

AU - Bizinelli, Daniela

AU - Kuasne, Hellen

AU - Barros Filho, Mateus Camargo

AU - Flores, Bianca Campos Troncarelli

AU - Pinto, Clóvis Antonio Lopes

AU - Rainho, Claudia Aparecida

AU - Soares, Milena Botelho Pereira

AU - Marchi, Fabio Albuquerque

AU - Kowalski, Luiz Paulo

AU - Rogatto, Silvia Regina

PY - 2023/11

Y1 - 2023/11

N2 - Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.

AB - Oral cavity squamous cell carcinoma (OSCC) is a complex and dynamic disease characterized by clinicopathological and molecular heterogeneity. Spatial and temporal heterogeneity of cell subpopulations has been associated with cancer progression and implicated in the prognosis and therapy response. Emerging evidence indicates that aberrant epigenetic profiles in OSCC may foster an immunosuppressive tumor microenvironment by modulating the expression of immune-related long non-coding RNAs (lncRNAs). DNA methylation analysis was performed in 46 matched OSCC and normal adjacent tissue samples using a genome-wide platform (Infinium HumanMethylation450 BeadChip). Reference-based computational deconvolution (MethylCIBERSORT) was applied to infer the immune cell composition of the bulk samples. The expression levels of genes encoding immune markers and differentially methylated lncRNAs were investigated using The Cancer Genome Atlas dataset. OSCC specimens presented distinct immune cell composition, including the enrichment of monocyte lineage cells, natural killer cells, cytotoxic T-lymphocytes, regulatory T-lymphocytes, and neutrophils. In contrast, B-lymphocytes, effector T-lymphocytes, and fibroblasts were diminished in tumor samples. The hypomethylation of three immune-associated lncRNAs (MEG3, MIR155HG, and WFDC21P) at individual CpG sites was confirmed by bisulfite-pyrosequencing. Also, the upregulation of a set of immune markers (FOXP3, GZMB, IL10, IL2RA, TGFB, IFNG, TDO2, IDO1, and HIF1A) was detected. The immune cell composition, immune markers alteration, and dysregulation of immune-associated lncRNAs reinforce the impact of the immune microenvironment in OSCC. These concurrent factors contribute to tumor heterogeneity, suggesting that epi-immunotherapy could be an efficient alternative to treat OSCC.

KW - Deconvolution

KW - DNA methylation

KW - LncRNAs

KW - Oral cancer

KW - Tumor immune microenvironment

U2 - 10.1016/j.biopha.2023.115559

DO - 10.1016/j.biopha.2023.115559

M3 - Journal article

C2 - 37742611

AN - SCOPUS:85171664022

SN - 0753-3322

VL - 167

JO - Biomedicine & Pharmacotherapy

JF - Biomedicine & Pharmacotherapy

M1 - 115559

ER -

DNA methylation-based depiction of the immune microenvironment and immune-associated long non-coding RNAs in oral cavity squamous cell carcinomas

Abstract

Bibliografisk note

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Fingeraftryk

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