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Expression of p27 and p16 and their clinical significance in gastric cancer

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Abstract

Background

Deregulated expression of cell cycle regulators p27 and p16 is associated with cancer progression. p27kip1 and p16INKa are a cyclin dependent kinase inhibitor whose major target is the cyclinE/CDK2 and cyclinD/CDK4/6 complex, respectively, that governs cell cycle transition from late G1 to S phase.

Methods

We recruited biopsies of a total of 84 subjects including 72 primary tumor biopsies from histopathologically proven gastric carcinoma, 8 adjacent controls and 12 independent controls. We used gastric cancer cell line, AGS, for validation of our data. Expression profiling at transcript level was done by semi-quantitative RT-PCR and at proteome level by immunohistochemistry and immunofluorescence. Receiver operator characteristics analysis was done for determining the diagnostic utility of p27 and p16 with respect to the sensitivity and specificity.

Results

We demonstrate that p27 and p16 are frequently over expressed in early stages of gastric carcinoma. Our semi-quantitative data show a significant upregulation of p27 (Mean ± SEM, 0.4771 ± 0.0895; p = 0.0001) and p16 (Mean ± SEM, 0.4676 ± 0.04305; p = 0.0001) at mRNA level. Concordant to semi-quantitative data, immunohistochemistry data also showed a significant upregulation of p27 (Mean ± SEM, 196.4 ± 10.84; p < 0.0001) and p16 (Mean ± SEM, 100.4 ± 23.71; p < 0.0001) at protein level.

Conclusions

The present study showed that the significant upregulation of p27 and p16 were associated with early events in gastric carcinogenesis. Our data suggests that clinical correlation of these differentially expressed genes may be useful as diagnostic biomarkers for early detection of gastric carcinoma and promising therapeutics target for GC patients.

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Acknowledgements

Authors acknowledge financial assistance from Department of Biotechnology (DBT), Ministry of Science and Technology, India to Dr. Puneet (BT/PR/11113/10/678/2008); Soni Kumari is thankful to DBT and Banaras Hindu University for Research Fellowships. Authors are thankful to Interdisciplinary School of Life Sciences, Banaras Hindu University and UGC-UPE programme of Banaras Hindu University for equipment facilities.

Funding

This study was funded by Department of Biotechnology, Government of India, vide Grant number BT/PR11113/BRB/10/678/ 2008 to Dr. Puneet and financial assistance from Banaras Hindu University to Soni Kumari.

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Authors and Affiliations

  1. Cancer Genetics Laboratory, Department of Molecular and Human Genetics, Faculty of Science, Banaras Hindu University, Varanasi, 221005, India

    S. Kumari & G. Narayan

  2. Department of Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    P. Kumar

  3. Department of Pathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, India

    M. Kumar

  4. Department of Zoology, Banaras Hindu University, Mahila Mahavidyalaya, Varanasi, 221 005, India

    S. Singh

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  1. S. Kumari
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Correspondence to P. Kumar.

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All procedures performed in studies involving human participants were in accordance with the 1964 Helsinki Declaration ethical standards and approved by the Institutional Ethical Committee of Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.

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Written informed consent was obtained from all individual participants included in the study.

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Kumari, S., Kumar, P., Kumar, M. et al. Expression of p27 and p16 and their clinical significance in gastric cancer. Clin Transl Oncol 23, 856–865 (2021). https://doi.org/10.1007/s12094-020-02479-4

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  • DOI: https://doi.org/10.1007/s12094-020-02479-4

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