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

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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.

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Data availability

Data used in this study can be obtained from corresponding author on special request. Data sets used for in-silico study can be assessed through GEO- NCBI website under the accession numbers provided in this study.

Abbreviations

CRC:

Colorectal cancer

MTDH:

Metadherin

MMPs:

Matrix metallo proteases

CIN:

Chromosomal instability

MSI:

Microsatellite instability

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Acknowledgements

Authors of this study are grateful to Higher Education Commission of Pakistan and COMSATS University, Islamabad for research facilitation for this study.

Funding

We are grateful to COMSATS University and HEC for needful funding and research support.

Author information

Author notes

  1. Aimen Sultan and Namood-e Sahar have contributed equally to this work.

Authors and Affiliations

  1. Department of Biosciences, COMSATS University Islamabad, Park Road, Islamabad, Pakistan

    Aimen Sultan, Namood-E Sahar, Javeria Qadir, Farhan Haq & Muhammad Faraz Arshad Malik

  2. College of Medicine, University of Nebraska, Medical Center, Omaha, USA

    Namood-E Sahar

  3. Department of Molecular Biology, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan

    Syeda Kiran Riaz

  4. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada

    Javeria Qadir

  5. Department of General Surgery, Shaheed Zulfiqar Ali Bhutto Medical University, Islamabad, Pakistan

    Shahzad Hussain Waqar & Tanwir Khaliq

Authors
  1. Aimen Sultan
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  2. Namood-E Sahar
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  8. Muhammad Faraz Arshad Malik
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Contributions

AS drafted the project, executed wet lab and in-silico experiments, performed micro array data analysis and statistical data analysis, prepared tables and figures and wrote the research paper. NES contributed equally and performed lab experiments, microarray data analysis study and revised the manuscript. SKR helped in data analysis and preparation of table and figures. JQ revised and edited the manuscript. SHW and TK performed surgeries and helped in sample collection. MFAM designed and supervised the study and reviewed the final draft of the manuscript.

Corresponding author

Correspondence to Muhammad Faraz Arshad Malik.

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Conflict of interest

The authors of the study have no conflict of interest to declare.

Ethical approval

In order to conduct this study, ethical consent was obtained from the Ethical Committees of Pakistan Institute of Medical Sciences (PIMS) hospital and COMSATS University Islamabad.

Consent to participate

Informed consents of all participants (patients) were obtained to conduct this study.

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All authors of the study showed agreement to publish this study in Molecular Biology Reports journal.

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Sultan, A., Sahar, NE., Riaz, S.K. et al. Metadherin (MTDH) overexpression significantly correlates with advanced tumor grade and stages among colorectal cancer patients. Mol Biol Rep 48, 7999–8007 (2021). https://doi.org/10.1007/s11033-021-06834-8

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  • DOI: https://doi.org/10.1007/s11033-021-06834-8

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