Aimen Sultan1, Namood-E Sahar1,2, Syeda Kiran Riaz3, Javeria Qadir1,4, Shahzad Hussain Waqar5, Farhan Haq1, Tanwir Khaliq5, Muhammad Faraz Arshad Malik6. 1. Department of Biosciences, COMSATS University Islamabad, Park Road, Islamabad, Pakistan. 2. College of Medicine, University of Nebraska, Medical Center, Omaha, USA. 3. Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan. 4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada. 5. Department of General Surgery, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan. 6. Department of Biosciences, COMSATS University Islamabad, Park Road, Islamabad, Pakistan. famalik@comsats.edu.pk.
Abstract
BACKGROUND: Colorectal cancer is the 4th leading cause of cancer related deaths affecting both men and women worldwide. In the present study, any probable role of MTDH mRNA expression in CRC tumorigenesis was explored using both discovery and validation cohorts. METHODS AND RESULTS: After prior ethical and biosafety approvals, tumor tissue samples along with their adjacent controls were collected for this study from Pakistani patients diagnosed with colorectal cancer. RNA was isolated using Trizol reagent, followed by cDNA synthesis. Transcript analysis of MTDH was performed by using qPCR. Moreover, genome-wide expression of MTDH was also determined through micro-array data analysis using BRB-array tools software. MTDH expression was significantly high in tumor tissue samples (p < 0.05) compared to their respective controls. Likewise, results of microarray analysis also revealed overamplification of MTDH in tumor samples as compared to controls. Expression of MTDH was also found to be positively correlated with KI-67 index (p < 0.05) and were observed to be significantly upregulated in advance tumor grade (p < 0.05) and stage (p < 0.05). However, no association of MTDH overexpression with age and gender could be established. CONCLUSION: Hence, it can be concluded that MTDH is a core element that plays a pivotal role in colorectal tumorigenesis irrespective of patient's age and gender. Molecular insight into the tumor microenvironment revealed MTDH as a niche, representing distinctive framework for cancer progression, thus, making it an innovative target strategy for colorectal cancer treatment.
BACKGROUND: Colorectal cancer is the 4th leading cause of cancer related deaths affecting both men and women worldwide. In the present study, any probable role of MTDH mRNA expression in CRC tumorigenesis was explored using both discovery and validation cohorts. METHODS AND RESULTS: After prior ethical and biosafety approvals, tumor tissue samples along with their adjacent controls were collected for this study from Pakistani patients diagnosed with colorectal cancer. RNA was isolated using Trizol reagent, followed by cDNA synthesis. Transcript analysis of MTDH was performed by using qPCR. Moreover, genome-wide expression of MTDH was also determined through micro-array data analysis using BRB-array tools software. MTDH expression was significantly high in tumor tissue samples (p < 0.05) compared to their respective controls. Likewise, results of microarray analysis also revealed overamplification of MTDH in tumor samples as compared to controls. Expression of MTDH was also found to be positively correlated with KI-67 index (p < 0.05) and were observed to be significantly upregulated in advance tumor grade (p < 0.05) and stage (p < 0.05). However, no association of MTDH overexpression with age and gender could be established. CONCLUSION: Hence, it can be concluded that MTDH is a core element that plays a pivotal role in colorectal tumorigenesis irrespective of patient's age and gender. Molecular insight into the tumor microenvironment revealed MTDH as a niche, representing distinctive framework for cancer progression, thus, making it an innovative target strategy for colorectal cancer treatment.