Rauf Ahmad WANI, Madiha NIYAZ, Mosin Saleem KHAN, Syed MUDASSAR, Aaliya SHAH, Omar Javid SHAH, Syed BESINA

Promoter Hypermethylation and Underexpression of Patched Homolog 1 in Pancreatic and Colorectal Cancers: A Cross-Sectional Study

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.

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