MLH۱ Gene expression and Pathologic factors in Iranian patients with Colorectal Cancer

Background and Aim: Colorectal cancer (CRC) is one of the most frequent cancers in humans, with about ۱.۲۳ million new cases diagnosed worldwide every year which is the fourth leading cause of cancer deaths worldwide, both men and women having approximately ۴.۳% CRC risk. MLH۱ is one of major part in heterodimeric complex MutLa, which is recognizes and repairs small loops in DNAeither by base–base mismatches or by insertion/deletion loops that arise from nucleotide misincorporation. Therefore, when the MLH۱ protein is absent or inactive, the number of errors that remain Unmodified during cell division will increase, and the cell will not be able to function properly and may cause tumors in the colon or other organs. The purpose of this study was quantitative analysis of MLH۱ gene expression in blood samples and its association with Depth of tumor invasion (T) and Lymph node invasion(N) factors in a number of Iranian patients with CRC.Methods: Blood samples from ۳۳ patients with colorectal cancer and ۳۳ normal cases were collected and extracted by RNA extraction (FAVORGEN BIOTECH CORP) kit and cDNA synthesis kit according to the protocol. PCR primers were designed by Exon-Exon Junction method and using Real-time quantitative polymerase chain reaction (qPCR) technique for MLH۱ and β-actin genes expression. Statistical analyses were performed using the software Rest۲۰۰۹ and T-test was used to evaluate the expression of MLH۱ gene and its association with Depth of tumor invasion (T) and Lymph node invasion(N) factors.Results: The results in ۳۳ patients with the average age of ۵۵ years by a frequency of ۴۷.۵% female and ۵۲.۵% male showed a significant decrease in MLH۱ gene expression in high stages of the disease (P <۰.۰۵ *). Reduction of expression in this gene is also associated with Depth of tumor invasion (T) (P <۰.۰۵ *) and Lymph node invasion(N) (P <۰.۰۵ *).Conclusion: In conclusion, the mRNA expression of MLH۱ in peripheral blood decrease in high stages of the CRC and showed associated with Depth of tumor invasion (T) and Lymph node invasion(N) factors in a number of Iranian patients with colorectal cancer. Due to the importance of the results, more samples should be considered for future research and their relationship with other clinical and pathological factors should be investigate. It may serve as a biomarker for the diagnosis of CRC.

Keywords:

Colorectal Cancer , Mismatch Repair Gene , MLH۱ , Gene expression , Real-time PCR