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Translational research/biomarkers
2022-RA-366-ESGO Calcium activated potassium channels (KCNMA1) as biomarker of pre invasive and invasive cervical cancer
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  1. Bindiya Gupta1,
  2. Puja Kumari2,
  3. Shalini Rajaram3,
  4. Rajarshi Kar4,
  5. Priyanka Gogoi5 and
  6. Sandhya Jain6
  1. 1Obstetrics and Gynecology, UCMS and GTB Hospital Delhi, Delhi, India
  2. 2Obstetrics and Gynecology, UCMS and GTB hospital, Delhi, India
  3. 3Obstetrics and Gynecology, AIIMS Rishikesh, Rishikesh, India
  4. 4Department of Biochemistry, UCMS and GTB hospital, Delhi, India
  5. 5Department of Pathology, UCMS and GTB hospital, Delhi, India
  6. 6UCMS and GTB hospital, Delhi, India

Abstract

Introduction With rising incidence of cervical cancer, novel biomarkers need to be developed. One such biomarker are ion channels and voltage gated channels which are known to be regulated by HPV oncogene and estradiol. Potassium channels including calcium- activated potassium channels (KCNMA1) are also involved in tumor cell proliferation, migration, invasion and angiogenesis and are over-expressed in cancers like glioma, breast, ovary and prostate. The primary objective was to study and compare the mRNA and protein expression of calcium-activated potassium channels (KCNMA1) in pre-invasive and invasive cervical cancer.

Methodology In a prospective comparative study women with biopsy proven diagnosis of CIN 1/2/3 and cervical carcinoma were recruited as cases (n=45). Cervical tissue from hysterectomy specimen done for benign gynaecological indication with normal cervical cancer screening tests were taken as controls (n=15). Women were allocated equally into four groups on the basis of histopathology, i.e. control (Group1), cervical intraepithelial neoplasia 1 (CIN1; Group2), CIN 2/3(Group 3) and invasive cervical carcinoma (Group 4). KCNMA1 mRNA level estimation was done by real-time quantitative PCR (RT-qPCR) and protein expression was studied by immunohistochemistry using anti- KCNMA1 rabbit polyclonal antibody against Maxi Potassium channel alpha. Main Outcome Measures estimated were KCNMA1 protein expression and mRNA expression in four groups: control, CIN1, CIN 2/3 and cervical cancer.

Results The mean KCNMA1 mRNA levels in Groups 1, 2, 3, 4 was 0.2253(SD±0.5798), 271.40(SD±1050.21), 298.84(SD±1153.33) and 326.545(SD±861.97) respectively; (p=0.039). Protein expression was positive in 34% in CIN1, 80% in CIN2/3 and 100% in the cervical cancer group(p≤0.001). On subgroup analysis in cancer, KCNMA1 channel mRNA levels and protein expression was higher in tumour size >4 cm, poorly differentiated tumours, deep stromal invasion and non keratinising squamous cell carcinoma.

Conclusion KCNMA1 channel expression has promising role as a biomarker of cervical precancer and cancer.

https://doi.org/10.1136/ijgc-2022-ESGO.866

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