Metadherin (MTDH) overexpression significantly correlates with advanced tumor grade and stages among colorectal cancer patients.

Aimen Sultan,Javeria Qadir,Syeda Kiran Riaz,Shahzad Hussain Waqar,Muhammad Faraz Arshad Malik,Namood-E Sahar,Tanwir Khaliq,Farhan Haq

doi:10.1007/s11033-021-06834-8

Abstract

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. 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. 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.

Highlights

Colorectal cancer is categorized among top three most common malignancies across the globe
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
In-line with these findings, validation cohort showed a similar trend in MTDH expression

Summary

Introduction

Colorectal cancer is categorized among top three most common malignancies across the globe. Incidence of colorectal cancer was frequently observed in countries with high Human development index. Pertinent studies have unveiled three main pathogenic mechanisms i.e., microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and chromosomal instability (CIN) pathway, to be responsible for 80-85% of CRC cases. Activation of these pathways have been linked with accretion of different mutations in several oncogenes and tumor suppressor genes such as SMAD2, BRAF, P53, EGF, MYC and RAS [2]. Being one of the most frequently activated oncogenes, RAS is considered as a prime key player in majority of colon cancer cases [3]. Any probable role of MTDH mRNA expression in CRC tumorigenesis was explored using both discovery and validation cohorts

Methods

Results

Conclusion