CSF1R methylation is a key regulatory mechanism of tumor‑associated macrophages in hepatocellular carcinoma

Cui,Bin; Fan,Xiaoxiao; Zhou,Daizhan; He,Lifeng; Li,Yirun; Li,Dandan; Lin,Hui

doi:10.3892/ol.2020.11726

CSF1R methylation is a key regulatory mechanism of tumor‑associated macrophages in hepatocellular carcinoma

Authors:
- Bin Cui
- Xiaoxiao Fan
- Daizhan Zhou
- Lifeng He
- Yirun Li
- Dandan Li
- Hui Lin
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Affiliations: China‑UK‑NYNU‑RRes Joint Laboratory of Insect Biology, Henan Key Laboratory of Insect Biology in Funiu Mountain, Nanyang Normal University, Nanyang, Henan 473061, P.R. China, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China
Published online on: June 11, 2020 https://doi.org/10.3892/ol.2020.11726
Pages: 1835-1845
Copyright : © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Tumor‑associated macrophages (TAMs) are important in tumor microenvironments and are closely associated with cancer occurrence, metastasis and progression. Colony stimulating factor 1 receptor (CSF1R) serves a crucial role in TAM formation. Whether CSF1R expression is regulated by DNA methylation in hepatocellular carcinoma (HCC) has not been fully elucidated. In the current study, HCC and adjacent non‑cancerous tissue (ANT) samples were collected from 160 patients with HCC. CSF1R methylation levels were analyzed using a Mass ARRAY Analyzer to establish the potential impact of CSF1R methylation alternations on HCC clinicopathological characteristics. The mean methylation level of the CSF1R promoter (chr 5:149492491‑149492958) was demonstrated to be significantly higher in ANTs compared with HCC tissues (65.3±7.5% vs. 57.3±14.4%, respectively; P<0.0001). CSF1R also exhibited decreased expression in HCC tissues compared with ANTs (P=0.0026). However, CSF1R expression was negatively correlated with CSF1R methylation levels in ANTs (r>0.4; P<0.0001). Further analysis indicated that patients with diabetes exhibited lower methylation levels in ANTs compared with HCC tissues (P=0.0062). Furthermore, CSF1R hypomethylation in ANTs was associated with a larger number of tumors (P=0.0332), larger tumor size (P=0.0494) and higher tumor grade (P=0.0244). Therefore, methylation alternation of the CSF1R promoter region analyzed in the present study was a key regulatory mechanism on CSF1R expression and ANT hypomethylation indicated poor clinicopathological characteristics of HCC. CSF1R may be a potential immunological therapeutic target for HCC.

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