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miRNA-200c and miRNA-141 as potential prognostic biomarkers and regulators of epithelial-mesenchymal transition in eyelid sebaceous gland carcinoma
  1. Mansi Bhardwaj1,
  2. Seema Sen1,
  3. Kunzang Chosdol2,
  4. Anjana Sharma3,
  5. Neelam Pushker4,
  6. Seema Kashyap1,
  7. Sameer Bakhshi5,
  8. Mandeep S Bajaj4
  1. 1Department of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  2. 2Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India
  3. 3Department of Ocular Microbiology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  4. 4Department of Ophthalmology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
  5. 5Department of Medical Oncology, Dr. B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India
  1. Correspondence to Professor Seema Sen, Room no. 725, Department of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi 110029, India; ssenop{at}rediffmail.com

Abstract

Background MicroRNA (miRNA)-200c and miRNA-141 are tumour suppressors, which regulate epithelial-mesenchymal transition (EMT), leading to tumour invasion and metastasis in various malignancies. miRNA-200c and miRNA-141 maintain the epithelial phenotype by post-transcriptionally inhibiting the E-cadherin repressors, zinc finger E-box binding homeobox (ZEB)1 and ZEB2. The present study was performed to determine the prognostic significance of miRNA-200c and miRNA-141, and their association with EMT markers ZEB1, ZEB2 and E-cadherin in eyelid sebaceous gland carcinoma (SGC).

Methods Expression levels of miRNA-200c and miRNA-141 were determined in 42 eyelid SGC cases by quantitative real-time PCR (qPCR). Their association with ZEB1, ZEB2 and E-cadherin was determined by qPCR and immunohistochemistry. Kaplan-Meier plots and Spearman's rank correlation tests were applied to analyse the data. Patients were followed up for 7–44 months.

Results Low expression levels of miRNA-200c and miRNA-141 were seen in 36/42 (86%) and 28/42 (67%) cases, respectively. Low miRNA-200c correlated significantly with large tumour size (p=0.03) and poor differentiation (p=0.03). Low miRNA-141 correlated significantly with large tumour size (p=0.02) and lymph node metastasis (p=0.04). Survival analysis revealed that patients with low miRNA-200c (p<0.05) and miRNA-141 expression (p=0.07) had shorter disease-free survival. There was a significant association of both miRNA-200c and miRNA-141 with E-cadherin and ZEB2 expression.

Conclusions Low levels of miRNA-200c and miRNA-141 in patients with eyelid SGC facilitates tumour progression by promoting EMT and miRNA-200c has emerged as a novel potential predictor of survival.

  • Eye Lids
  • Pathology
  • Experimental &#8211 laboratory
  • Neoplasia

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Footnotes

  • Contributors MB: data collection, analysis, interpretation and writing. SS, KC and AS: conception and design. SK, NP, MSB and SB: acquisition of clinical data.

  • Funding Supported by All India Institute of Medical Sciences (grant F.5-59/IRG/2010/RS) and Indian Council of Medical Research (grant 3/2/2/240/2014-NCD-III) for financial support.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval This study was conducted after approval from the Institute Ethics Committee, AIIMS, New Delhi (Ref. No. IESC/NP-221/2012) and carried out in accordance with Declaration of Helsinki principles. Informed consent was obtained from all patients participating in this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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