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Impacts of some clinicopathodemography and colorectal tissues key cell cycle and mucin stabilizing molecules on the metastasis trend in colorectal cancer patients

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Abstract

Background

We aimed to evaluate the various clinicopathodemographical, epidemiological, and molecular contributors to cumulatively worldwide metastatic colorectal cancer (CRC) in CRC patients from a highly populated area in northeastern Iran to pinpoint metastasis risk.

Methods

A retrospective clinical material-based cohort including a total of 6260 registered CRC patients, of whom 3829 underwent surgery, from regional university hospitals, during 2006–2016, were analyzed for the clinicopathodemographical aspects of age, sex, stage of CRC, history of smoking, type 2 diabetes (T2D), hypertension, body mass index (BMI), familial/occupational status, post-surgery survival period and mRNA/protein expression of mucin stabilizer (B3GALNT2), mucin I (MUC1), key cell cycle molecules (i.e., P53 and Ki67), and MMR-related genes. Factors were set to estimate the risk of metastatic CRC and mortality.

Results

Predominant adenocarcinomatous CRCs were found in colon. Post-surgery survival period of metastatic CRC patients was remarkably longer in patients aged > 50 compared to those aged < 50 years, and worse in females than males. B3GALNT2high, MUChigh, P53low, and Ki67high mRNA/protein expression in the metastatic stage III CRC along with T2D and hypertension were associated with increased metastasis/mortality, with more worsening in males, older, BMI > 25, urban residing, and employed individuals, indicative of non-genetic attributable factors.

Conclusion

B3GALNT2, MUC1, and “Ki67” can be used as promising biomarkers for prognosis and early diagnosis of increasingly/predominantly non-genetic/environmental originated metastatic CRCs.

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Data availability

All data are available in this article and supporting file.

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Acknowledgements

The authors appreciate the supports from Ferdowsi University of Mashhad and University of Tehran. We are grateful to Dr. Per Hydbring for critically reading and editing the manuscript. Part of this manuscript was submitted and then rejected in BMC Cancer, but mistakenly appeared/viewed at the Research Square as a pre-print54, which should have been removed from the Research Square; simultaneously, after rejection we further worked, did more assays, and improved the quality of manuscript for publication.

Funding

This study was (along with specific funding from the main investigator) partially supported from the Ferdowsi University of Mashhad and University of Tehran.

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Authors and Affiliations

  1. Department of Pathobiology, Section Biotechnology, Faculty of Veterinary Medicine, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Ali Ghorbani Ranjbary

  2. Department of Microbiology and Immunology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

    Ali Ghorbani Ranjbary, Jalil Mehrzad & Nasrollah Rahbar

  3. Department of Basic Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran

    Hesam Dehghani

  4. Stem Cells and Regenerative Medicine Research Group, Research Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Hesam Dehghani

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Contributions

AGR and JM collected the data, performed the treatments, and designed, wrote, and finalized the study. JM was also responsible for paper and for its supervision. NR and HD reviewed statistical analyses, supported the data collection, and critically revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jalil Mehrzad.

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The authors declare that they have no competing interests.

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The study protocol has been approved by the ethical committee of Mashhad University of Medical Sciences with the commitment of the principles of the declaration of Helsinki.

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Ghorbani Ranjbary, A., Mehrzad, J., Rahbar, N. et al. Impacts of some clinicopathodemography and colorectal tissues key cell cycle and mucin stabilizing molecules on the metastasis trend in colorectal cancer patients. Mol Biol Rep 50, 8589–8601 (2023). https://doi.org/10.1007/s11033-023-08766-x

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