Recognition of bone metastasis driving genes in hepatocellular carcinoma by machine learning and analysis of in external-beam radiotherapy

Abstract

Abstract: Objective:To identify the driving genes of hepatocellular carcinoma with bone metastasis (HCC-BM) by machine learning and to explore the effect of external-beam radiotherapy (EBRT) on the expression level of driving genes.
Methods:GSE14520 and GSE84402 data sets in Gene Expression Omnibus database were combined as test sets, and GSE121248 andGSE54236 data sets were used as validation sets respectively. The least absolute shrinkage and selection operator and support vector machine-regression feature elimination were performed to screen the key differentially expressed genes,and the intersection with HCC-BM related genes in the GeneCards database obtained HCC-BM driving genes. CIBERSORT evaluated the correlation between HCC-BM driver gene and immune cell infiltration.The 22 HCC-BM patients admitted to our hospital from 2020 to 2021 were selected as the study group. In the same period, 22 healthy people with normal physical examinations in our hospital were selected as the control group. The changes in HCC-BM driver gene expression before and after EBRT were compared, and the relationship between HCC-BM driver gene expression and and relationship with ASPM expression levels and pain relief.
Results:Four HCC-BM driving genes were identified,it is respectively assembly factor for spindle microtubules (ASPM), C-type lectin domain family 4 member M (CLEC4M), extracellular matrix protein 1 (ECM1), and ficolin 2 (FCN2). The expression of ASPM in normal liver tissue was lower than that in HCC tissue (P<0.05), and the expression of clec4m, ECM1, and FCN2 was higher than that in HCC tissue (P<0.05). The same results were obtained in both validation sets GSE121248 and GSE54236. The prognosis of HCC patients with high ASPM expression is poor, while patients with low CLEC4M, ECM1 and FCN2 expression are better. ASPM was positively correlated with macrophages m2; CLEC4M was positively correlated with macrophages M2, neutrophils, and M1 macrophages; FCN2 was negatively correlated with macrophages M0. The expression of serum ASPM in 22 patients with HCC-BM was higher than that in the healthy control group (P < 0.05), and the expression of FCN2 was lower than that in the healthy control group (P<0.05). After EBRT, the expression level of serum ASPM in HCC-BM patients decreased (P<0.05). The expression level of serum ASPM in patients with complete remission was lower than that in patients with partial remission.
Conclusions:ASPM, CLEC4M, ECM1, and FCN2 may be involved in the pathogenesis of HCC-BM. Among them, ASPM may be related to the effect of EBRT. Further exploration of driver genes is helpful to develop therapeutic targets, improve the effect of EBRT and then improve the prognosis.

Key words: Hepatocellular carcinoma, Bone metastasis, Immune cells, Extracorporeal radiotherapy, Prognosis

Wang Yu, Tong Liexing, Kang Wanying, Ding Xin, Qian Hesheng. Recognition of bone metastasis driving genes in hepatocellular carcinoma by machine learning and analysis of in external-beam radiotherapy[J]. Electronic Journal of Liver Tumor, 2023, 10(3): 64-75.

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