2Department of Biochemistry, Sher-I-Kashmir Institute of Medical Sciences Medical College, Srinagar-India
3Department of General and Minimal Invasive Surgery, Sher-I-Kashmir Institute of Medical Sciences, Srinagar-India
4Department of Surgical Gastroenterology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar-India
5Department of Pathology, Sher-I-Kashmir Institute of Medical Sciences, Srinagar-India DOI : 10.5505/tjo.2021.2890 OBJECTIVE
Patched homolog 1 (PTCH1) - a trans-membrane protein is a tumor suppressor which negatively regulates Hedgehog signaling pathway. The present study aimed to investigate the promoter hypermethylation and protein expression pattern of PTCH1 in Pancreatic cancer (PC) and Colorectal cancer (CRC).
METHODS
Promoter hypermethylation of PTCH1 gene was analyzed using Methylation-Specific Polymerase Chain
Reaction and protein expression pattern was studied using western blotting.
RESULTS
Promoter hypermethylation of the PTCH1 gene was found in 42.42% (14/33) and 55.73% (34/61) of
Pancreatic and Colorectal tumor samples, respectively. A significant correlation was found between
PTCH1 hypermethylation and smoking status in PC while PTCH1 hypermethylation in CRC was significantly
correlated with late-stage disease and lymph node metastasis. PTCH1 protein was under expressed
in 30.3% (10/33) and 50.8 % (31/61) of Pancreatic and Colorectal tumor samples, respectively.
Methylation analysis of PTCH1 in Pancreatic adenocarcinoma cell line 1 (PANC-1) and Colorectal adenocarcinoma
cell line (HT-29) revealed hemi methylation in PANC-1, complete methylation in HT-29
and methylation was clearly associated with loss of expression.
CONCLUSION
Our results indicate that epigenetic silencing of the PTCH1 promoter and concomitant loss of PTCH1
protein expression may play an important role in the development and progression of these cancers.