p16 ^INK4a Promoter Hypermethylation in Gallbladder Cancer

Gallbladder cancer (GBC) is a deadly cancer with a widely disparate occurrence rate across the world. p16INK4a is a tumor-suppressor gene and its silencing has been reported to be quite important in carcinogenesis of a variety of cancers like lung, pancreas, stomach including less so in GBC. The lack of gene function linked with abnormal methylation provides selective growth advantages to sporadic neoplastic cells during GBC carcinogenesis. The methylation status of the p16INK4a gene was assessed using methylation-specific polymerase chain reaction (MSP) in fresh tissue samples from 53 GBC (cases) and 39 patients with gallstone disease (GSD) (controls) obtained from Indian patients posted for surgery in a tertiary care hospital in northern India. In 56.6% of the GBC samples, abnormal methylation of the p16INK4a gene was found, compared to none in patients with GSD. p16INK4a methylation was found to be significantly associated with GBC stage and grade [P = 0.001, OR = 60.745, 95% CI = 4.888-754.896 and P = 0.012, OR = 21.036, 95% CI = 1,976-223.946], respectively. The area under the ROC curve was 0.875 and 0.871 with advanced stage and grade respectively. These data suggest that p16INK4a hypermethylation is a common occurrence in GBC and is probably associated with an aggressive phenotype of GBC.

The online version contains supplementary material available at https://doi.org/10.1007/s13193-025-02500-8.