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Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma

Pathology & Oncology Research volume 24, pages 207–214 (2018)Cite this article

Abstract

Large tumor suppressor (LATS) is an important member of the Hippo pathway which can regulate organ size and cell proliferation. However, very little is known about the expression and clinical significance of LATS in lung cancer especially from this part of the world. We elucidated the frequency of LATS1 &LATS2 promoter hypermethylation (by methylation-specific PCR) and expression (by real-time PCR) in sixty nine (n = 69) Non-Small Cell Lung Cancer (NSCLC) patients and their corresponding normal lung tissue samples. We found promoter hypermethylation frequencies of LATS1 & LATS1to be 66.66% (46/69) and 71% (49/69) in NSCLC tissues. Decreased LATS1 & LATS2 mRNA expression was found in 55% and 66.66% of NSCLC patients. The LATS1 mRNA expression was significantly higher in normal lung tissues. Also, the mRNA levels of LATS1 and LATS2 NSCLC tissues with hypermethylation were significantly lower. Multivariable analysis confirmed that LATS1 under expression increased the hazard of death after adjusting for other clinicopathological factors. Importantly, the loss of LATS1 mRNA expression was associated with overall short survival. LATS1 is an independent prognostic factor and may play an important role in NSCLC progression and may serve as a novel therapeutic target of NSCLC.

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Acknowledgements

The authors gratefully acknowledge the Technical Staff of the operation theater of Department of CVTS. This study was supported by Sher-I-Kashmir Institute of Medical Sciences (SKIMS), Soura, Srinagar, Kashmir 190011, India (Grant no# No.SIMS/ACAD/14-786).

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Affiliations

  1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, 190011, India

    Showkat A. Malik, Mosin S. Khan, Mohammad A. Shah, Sheikh M. Shafi & Syed Mudassar

  2. Department of Cardiovascular and Thoracic Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, India

    Majeed Dar

  3. Department of Biotechnology, University of Kashmir, Srinagar, 190006, India

    Mahboob Ul Hussain

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  1. Showkat A. Malik
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  2. Mosin S. Khan
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  3. Majeed Dar
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  4. Mahboob Ul Hussain
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Correspondence to Syed Mudassar.

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Malik, S.A., Khan, M.S., Dar, M. et al. Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma. Pathol. Oncol. Res. 24, 207–214 (2018). https://doi.org/10.1007/s12253-017-0225-3

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  • DOI: https://doi.org/10.1007/s12253-017-0225-3

Keywords

  • Lung cancer
  • Survival
  • Hazard ratio
  • Non-small cell lung cancer
  • LATS1
  • LATS2