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Calcium-Activated Potassium Channel (KCNMA1) as Biomarker of Pre-Invasive and Invasive Cervical Cancer

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Abstract

Purpose of the Study

Several ion channels including calcium-activated potassium channels like KCNMA1 have been proposed as tumor markers and therapeutic targets for various cancers. KCNMA1 channel expression has been found to be progressively increasing with increasing severity of the lesion in samples collected retrospectively. Therefore, we aimed to prospectively study the mRNA and protein expression of KCNMA1 in pre-invasive and invasive cervical cancer.

Methods

Sixty women were recruited to the study and allocated equally (n = 15) into four groups on the basis of histopathology, i.e., control (Group 1), cervical intraepithelial neoplasia CIN1 (Group 2), CIN2/CIN3 (Group 3) and invasive cervical carcinoma (Group 4). Real-time PCR and immunohistochemistry were used for assessing mRNA and protein expression of KCNMA1 at mRNA and protein level, respectively.

Results

The mean KCNMA1 mRNA levels in Groups 1, 2, 3 and 4 were 0.23 (SD ± 0.58), 271.40 (SD ± 1050.21), 298.84 (SD ± 1153.33) and 326.54 (SD ± 861.97), respectively (p = 0.039). Protein expression was positive in 34% in CIN1, 80% in CIN2/CIN3 and 100% in the cervical cancer group (p = < 0.001). On subgroup analysis in cervical cancer, KCNMA1 mRNA and protein expressions were higher in tumor size > 4 cm, poorly differentiated tumors, deep stromal invasion and non-keratinizing squamous cell carcinoma.

Conclusions

KCNMA1 protein and mRNA expressions were significantly different between the groups studied. The expression was found to increase with severity of lesion. To the best of our knowledge, this is the first prospective study on KCNMA1 channels in cervical pre-cancer and cancer. Further exploratory studies can be done to establish KCNMA1 as a prognostic biomarker.

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References

  1. World Health Organization (WHO). Estimated age-standardized incidence and mortality rates World) in 2020, cervix uteri, females, all ages. Globocan 2020. Available at: https://gco.iarc.fr. Accessed 16 April 2021

  2. Schiffman M, Doorbar J, Wentzensen N, de Sanjosé S, Fakhry C, Monk BJ, Stanley MA, Franceschi S. Carcinogenic human papillomavirus infection. Nat Rev Dis Primers. 2016;2:16086.

    Article  PubMed  Google Scholar 

  3. Au WW, Abdou-Salama S, Sierra-Torres CH, Al-Hendy A. Environmental risk factors for prevention and molecular intervention of cervical cancer. Int J Hyg Environ Health. 2007;210(6):671–8.

    Article  PubMed  Google Scholar 

  4. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. A transmembrane intracellularestrogen receptor mediates rapid cell signaling. Science. 2005;307:1625–30.

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Chen D, Carter TH, Auborn KJ. Apoptosis ofcervical cancer cells: implications for adjunct antiestrogentherapy for cervical cancer. Anticancer Res. 2004;24:2649–56.

    CAS  PubMed  Google Scholar 

  6. Brake T, Lambert PF. Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model. Proc Natl Acad Sci USA. 2005;102(7):2490–5. https://doi.org/10.1073/pnas.0409883102. (Epub 2005 Feb 7. PMID: 15699322; PMCID: PMC548999).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Reuschenbach M, von Knebel DM. Diagnostic tests for the detection of human papillomavirus-associated cervical lesions. Curr Curr Pharm Des. 2013;19(8):1358–70.

    CAS  PubMed  Google Scholar 

  8. Chen Y, Cui Z, Xiao Z, Hu M, Jiang C, Lin Y, Chen Y. PAX1 and SOX1 methylation as an initial screening method for cervical cancer: a meta-analysis of individual studies in Asians. Ann Transl Med. 2016;4(19):365.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rodríguez-Rasgado JA, Acuña-Macías I, Camacho J. Eag1 channels as potential cancer biomarkers. Sensors (Basel). 2012;12(5):5986–95.

    Article  ADS  PubMed  Google Scholar 

  10. VázquezSánchez AY, Hinojosa LM, ParraguirreMartínez S, González A, Morales F, Montalvo G, et al. Expression of KATP channels in human cervical cancer: potential tools for diagnosis and therapy. Oncol Lett. 2018;15:6302–8.

    PubMed  Google Scholar 

  11. Pardo LA, Stühmer W. The roles of K (+) channels in cancer. Nat Rev Cancer. 2014;14:3948.

    Article  Google Scholar 

  12. Oeggerli M, Tian Y, Ruiz C, Wijker B, Sauter G, Obermann E, et al. Role of KCNMA1 in breast cancer. PLoS ONE. 2012;7: e41664.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bloch M, Ousingsawat J, Simon R, Schraml P, Gasser TC, Mihatsch MJ, et al. KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer. Oncogene. 2007;26(17):2525–34.

    Article  CAS  PubMed  Google Scholar 

  14. Ramírez A, Vera E, Gamboa-Domínguez A, Lambert P, Gariglio P, Camacho J. Calcium-activated potassium channels as potential early markers of human cervical cancer. Oncol Lett. 2018;15(5):7249–54.

    PubMed  PubMed Central  Google Scholar 

  15. D’Amico M, Gasparoli L, Arcangeli A. Potassium channels: novel emerging biomarkers and targets for therapy in cancer. Recent Pat Anticancer Drug Discov. 2013;8(1):53–65. https://doi.org/10.2174/15748928130106. (PMID: 22574647).

    Article  CAS  PubMed  Google Scholar 

  16. Sun X, Li Y, Lan H, Jiang T, Wan X, Cheng Y. Identification of KCNK1 as a potential prognostic biomarker and therapeutic target of breast cancer. Pathol Res Pract. 2023;241: 154286. https://doi.org/10.1016/j.prp.2022.154286. (Epub 2022 Dec 20. PMID: 36566598).

    Article  CAS  PubMed  Google Scholar 

  17. Wen J, Lin B, Lin L, Chen Y, Wang O. KCNN4 is a diagnostic and prognostic biomarker that promotes papillary thyroid cancer progression. Aging (Albany NY). 2020;12(16):16437–56. https://doi.org/10.18632/aging.103710.

    Article  CAS  PubMed  Google Scholar 

  18. Mazar J, DeYoung K, Khaitan D, Meister E, Almodovar A, Goydos J, et al. The regulation of miRNA-211 expression and its role in melanoma cell invasiveness. PLoS ONE. 2010;5(11): e13779.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  19. Tang T, Wong HK, Gu W, Yu MY, To KF, Wang CC, et al. MicroRNA-182 plays an onco-miRNA role in cervical cancer. Gynecol Oncol. 2013;129(1):199–208.

    Article  CAS  PubMed  Google Scholar 

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Funding

The authors declare that no funds, grants or other support were received during the preparation of this manuscript.

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Authors and Affiliations

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Contributions

Kumari P and Parveen N were responsible for protocol/project development, data collection or management, data analysis and manuscript writing/editing. Gupta B was involved in protocol/project development, data collection or management, data analysis, manuscript writing/editing and critical revision of manuscript. Rajaram S and Sandhya Jain contributed to protocol/project development, manuscript writing/editing and critical revision of manuscript. Kar R took part in data collection or management, data analysis and critical revision of manuscript. Gogoi P participated in data collection or management, data analysis and manuscript writing/editing. Mudassir M assisted with data analysis, manuscript writing/editing and critical revision of manuscript.

Corresponding author

Correspondence to Bindiya Gupta.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Ethical approval was taken from the Institutional Ethics Committee—Human Research (IEC-HR), University College of Medical Science, University of Delhi, Delhi 95 (Letter No. IEC-HR/2018/36/85R).

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Kumari, P., Parveen, N., Gupta, B. et al. Calcium-Activated Potassium Channel (KCNMA1) as Biomarker of Pre-Invasive and Invasive Cervical Cancer. Indian J Gynecol Oncolog 22, 40 (2024). https://doi.org/10.1007/s40944-024-00822-z

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  • DOI: https://doi.org/10.1007/s40944-024-00822-z

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