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.