Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

Jiawei Dong; Jiawei Dong; Fang Wang; Fang Wang; Xin Gao; Hongtao Zhao; Hongtao Zhao; Jiheng Zhang; Jiheng Zhang; Nan Wang; Nan Wang; Zhihui Liu; Zhihui Liu; Xiuwei Yan; Xiuwei Yan; Jiaqi Jin; Jiaqi Jin; Yixu Ba; Yixu Ba; Shuai Ma; Shuai Ma; Jianyang Du; Hang Ji; Hang Ji; Shaoshan Hu; Shaoshan Hu

doi:10.3389/fonc.2022.977251

Frontiers in Oncology (Jan 2023)

Integrated analysis of genome-wide DNA methylation and cancer-associated fibroblasts identified prognostic biomarkers and immune checkpoint blockade in lower grade gliomas

Jiawei Dong,
Jiawei Dong,
Fang Wang,
Fang Wang,
Xin Gao,
Hongtao Zhao,
Hongtao Zhao,
Jiheng Zhang,
Jiheng Zhang,
Nan Wang,
Nan Wang,
Zhihui Liu,
Zhihui Liu,
Xiuwei Yan,
Xiuwei Yan,
Jiaqi Jin,
Jiaqi Jin,
Yixu Ba,
Yixu Ba,
Shuai Ma,
Shuai Ma,
Jianyang Du,
Hang Ji,
Hang Ji,
Shaoshan Hu,
Shaoshan Hu

Affiliations

Jiawei Dong: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Jiawei Dong: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Fang Wang: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Fang Wang: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Xin Gao: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Hongtao Zhao: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Hongtao Zhao: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Jiheng Zhang: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Jiheng Zhang: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Nan Wang: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Nan Wang: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Zhihui Liu: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Zhihui Liu: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Xiuwei Yan: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Xiuwei Yan: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Jiaqi Jin: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Jiaqi Jin: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Yixu Ba: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Yixu Ba: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Shuai Ma: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Shuai Ma: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Jianyang Du: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Hang Ji: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Hang Ji: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China
Shaoshan Hu: Cancer Center, Department of Neurosurgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
Shaoshan Hu: Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China

DOI: https://doi.org/10.3389/fonc.2022.977251
Journal volume & issue: Vol. 12

Abstract

Read online

BackgroundCancer-associated fibroblasts (CAFs) are vital components of prominent cellular components in lower-grade gliomas (LGGs) that contribute to LGGs’ progression, treatment resistance, and immunosuppression. Epigenetic modification and immunity have significant implications for tumorigenesis and development.MethodsWe combined aberrant methylation and CAFs abundances to build a prognostic model and the impact on the biological properties of LGGs. Grouping based on the median CAFs abundances score of samples in the TCGA-LGGs dataset, differentially expressed genes and aberrantly methylated genes were combined for subsequent analysis.ResultsWe identified five differentially methylated and expressed genes (LAT32, SWAP70, GSAP, EMP3, and SLC2A10) and established a prognostic gene signature validated in the CGGA-LGGs dataset. Immunohistochemistry (IHC) and in vitro tests were performed to verify these expressions. The high-risk group increased in tumor-promoting immune cells and tumor mutational burden. Notably, risk stratification had different ICB sensitivities in LGGs, and there were also significant sensitivity differences for temozolomide and the other three novel chemotherapeutic agents.ConclusionOur study reveals characteristics of CAFs in LGGs, refines the direct link between epigenetics and tumor stroma, and might provide clinical implications for guiding tailored anti-CAFs therapy in combination with immunotherapy for LGGs patients.

Published in Frontiers in Oncology

ISSN: 2234-943X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.frontiersin.org/journals/oncology/

About the journal

Abstract

Keywords