Table 2.
Effect of DNA Promoter Methylation Modification of Diverse Genes on HCC
| Gene Site | Methylated Target Genes | Promoter Methylation Status | Influence on Self-Expression | Mechanisms on HCC |
|---|---|---|---|---|
| NC_000001. 11 | PIGC | Hyper | Inhibit | An oncogene and its hypermethylation inhibits HCC development66 |
| CDH5 | Hyper | Inhibit | Potential tumor suppressor genes, hypermethylation improve the occurrence and development of HCC67 | |
| RAB42 | Hypo | Promote | A potent prognostic biomarker for HCC68 | |
| WASF2 | Hypo | Promote | Hypomethylation boosts HCC proliferation, and WASF2 inactivation leads to tumor suppression in vitro52 | |
| LINE-1 | Hypo | Promote | Hypomethylation can inadvertently lead to the activation of various tumor promoting genes, it identified as an independent prognostic factor for overall survival and disease progression56,69 |
|
| NC_000003. 12 | VIPR1 | Hyper | Inhibit | VIPR1 transcriptional silencing caused by DNA methylation may contribute to the initiation and progression of HCC70 |
| MUC13 | Hypo | Promote | Positive effect on the production of CSCs and promotes the carcinogenesis of liver cells55 | |
| HDAC11 | Hypo | Promote | Improving HCC progression, related to sorafenib chemotherapy resistance53 | |
| NC_000004. 12 | SFRP2 | Hyper | Inhibit | Significantly elevated in poorly differentiated HCC and is an independent risk factor for the development of HCC, it is expected to be used as a non-invasive diagnostic biomarker for HBV-HCC71 |
| CDKL2 | Hyper | Inhibit | Hypermethylation status has high specificity and sensitivity for distinguishing adjacent paracancerous tissues from HCC tissues72 | |
| NC_000005. 10 | APC | Hyper | Promote | APC inhibits tumor growth and reduces the proportion of microvascular invasion48 |
| VTRNA2-1 | Hyper | Inhibit | The hypermethylation status of the promoter is strongly associated with tumor size, pathological vascular invasion, tumor recurrence, and more advanced tumor stage42 | |
| CSF1R | Hypo | Independent of the level of expression | Related to tumor stage and degree of malignancy35 | |
| NC_000007. 14 | STEAP4 | Hyper | Inhibit | Inhibits the proliferation and metastasis of HCC cells and mediates the biological effects of HCC cells through the inhibition of the PI3K/AKT/mTOR pathway44 |
| NC_000008. 11 | ADRA1A | Hyper | Inhibit | Low expression promoter was significantly in connection with alcohol intake, AFP and cirrhosis, but not link to TNM stage73 |
| NC_000009. 12 | RECK | Hyper | Inhibit | Promoter hypermethylation is linked with HCV-HCC, and varying degrees of methylation are engaged with serum RECK levels, lymph node metastasis, and vascular infiltration49 |
| GLDC | Hypo | Promote | Promote the invasion and proliferation of liver cancer74 | |
| NC_000011. 10 | ATM | Hyper | Inhibit | Encouraging HCC development, possibly increasing the risk of HCC by regulating ATM expression73 |
| KCNQ1 | Hyper | Inhibit | Tumor suppressor factor, and its expression is reduced to inhibit liver cancer metastasis75 | |
| CCND1 | Hypo | Promote | Prospective diagnostic marker in patients with AFP-negative HBV-HCC and AFP-positive CHB57 | |
| NC_000012. 12 | USP44 | Hyper | Unmethylated in normal tissues, hypermethylated only in HCC tissues76 | |
| NKG2D | Hyper | Inhibit | Has good predictive value for HCC diagnosis62 | |
| PZP | Hyper | Inhibit | PZP significantly inhibits the proliferation, invasion and migration of HCC cells77 | |
| NC_000013. 11 | PCDH17 | Hyper | Inhibit | Regulate EMT and cell proliferation related proteins, influences the biological behavior of HCC and inhibits HCC Proliferation and progression60 |
| SPG20 | Hyper | Hypermethylation status is significantly possessing intrahepatic metastasis and results in HCC metastasis72 | ||
| NC_000016. 10 | JPH3 | Hyper | Tumor suppressors, affect the EMT of HCC cells51 | |
| CDH13 | Hyper | Inhibit | Tumor suppressor gene, methylation in HCC is significantly increased78 | |
| NC_000017. 11 | Sox15 | Hyper | Inhibit | Tumor suppressor genes, down regulation of Wnt pathway and its target gene suppression47 |
| TMEM106A | Hyper | Inhibit | Downward regulated predictions have a poor prognosis, and their levels distinguish between tumor and paracancerous tissues79 | |
| SEPT9 | Hyper | Promote | Predict MVI and tumor proliferation in HCC, and plasma mSEPT9 can be used as an excellent biomarker for HCC diagnosis and early detection in clinical settings80,81 | |
| RNF135 | Hyper | Inhibit | Independent predictor of poor prognosis in patients with HCC82 | |
| NC_000020. 11 | NAAT | Hyper | Phosphorylation of LKB3 and PTEN was altered to regulate the PI3K-Akt signaling pathway and promote HCC development17 | |
| CTCFL | Hypo | Hypomethylation differs significantly from benign lesion samples, shortened survival, and increased vascular involvement54 | ||
| NC_000023. 11 | ZCCHC13 | Hypo | Promote | Promotes G1-S transition and promotes cell cycle progression, associated with abnormal activation of ATK/ERK/c-MYC/CDK pathway58 |