In this study, we demonstrated that necrosis-inducing peptide P16 kills human glioblastoma cancer cells and primary human hepatoma or renal cancer cells isolated from patients who had not responded to standard treatments.
The expression of FHIT and p16 genes and proteins in HCC tissues were obviously lower than those in cancer-adjacent tissues (P<0.05 in all comparisons).
Compared with paracancerous tissue, normal liver tissue, cirrhosis, and chronic hepatitis B as controls, the pooled ORs of P16 promoter region methylation in HBV-related HCC cancer tissues were 7.18 (95% CI =2.31-22.33), 24.89 (95% CI =3.38-183.03), 5.92 (95% CI =1.78-19.68), and 12.12 (95% CI =0.75-196.50).
<b>Conclusions:</b> HCC pathogenesis affecting p16 methylation don't work during normal blood, when from benign diseases to HCC bloods, can produce powerful role.
As the data suggested, multivariate cox regression analysis revealed that the recurrence-free survival of 46 patients was greatly associated with portal vein tumor thrombus (PVTT) and p16 methylation and receiver operating characteristic (ROC) curves demonstrated that the predictive range of portal vein tumor thrombus (PVTT) combined with p16 hypermethylation was more sensitive than that of either PVTT or p16 hypermethylation alone with regard to disease recurrence in patients with HCC, which could be testified as a valuable biomarker in Clinical application.
No association was found between p16 methylation or alteration and the prognosis of patients with HCC in overall survival (OS) and disease-free survival (DFS).
In vitro experiments using the human HCC cell lines revealed that K19 silencing suppressed cell growth by inducting apoptosis or upregulating p16 and p27, resulting in cellular senescence.
In addition, we identified a potential role for nuclear-cytoplasmic shuttling in p16-stimulated migration, consistent with the predominantly cytoplasmic localization of p16 in IHC-positive HCC samples.
P16 hypermethylation induces the inactivation of p16 gene, plays an important role in hepatocarcinogenesis, and is associated with an increased risk of HCC and liver cirrhosis.
The difference of CDKN2A-methylation and p16 protein expression between HCCs and liver metastases was statistically significant (p < 0.01, respectively).
Since loss of p16 is closely related to functional inactivation of p27 in HCC, investigating both p16 and p27 may be useful for precise prognostic predictions in individuals with HCC.
However, p16 methylation was associated with a poor survival after surgery for recurrent stage I to II hepatocellular carcinomas (hazard ratio, 4.05; 95% confidence interval, 1.15-14.20; P = 0.03).
The hypermethylation frequency of GSTP1 and RASSF1A showed significant difference between HCCs and liver cirrhosis with or without HBV infection (P<0.05), but differences of the hypermethylation status of APC, E-cadherin, and P16 were not statistically significant.
The results in this study also showed that the frequency of antibodies to p16 is relatively higher in nasopharyngeal cancer (28.6%), breast cancer (17.1%) and hepatocellular carcinoma (HCC, 21.4%).