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Expression Analysis Elucidates the Roles of MAML1 and Twist1 in Esophageal Squamous Cell Carcinoma Aggressiveness and Metastasis

  • Thoracic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Epithelial-mesenchymal transition has recently attracted great attention in studying the malignant progression of cells through a converging pathway of oncogenesis and metastasis. Twist1 and Mastermind-like 1 (MAML1) are major regulators of EMT through different pathways. The aim of this study was to investigate the clinicopathological relevance of the expression of MAML-1 and Twist1 genes in esophageal squamous cell carcinoma (ESCC).

Methods

Tumoral and corresponding normal tissues from 55 treatment-naive ESCC patients were subjected for expression analysis with quantitative real-time RT-PCR.

Results

Overexpression of MAML-1 and Twist1 were significantly associated with lymph node metastasis and the surgical staging of tumor. Overexpression of Twist1 was associated with tumor depth of invasion. Mean relative expression (MRE) of MAML1 was significantly higher in patients with metastasis to lymph nodes (3.07 ± 0.51 vs. 0.86 ± 0.58, P = .008). MRE of Twist1 was significantly higher in patients with invasion of tumor to adventitia (T3, T4) (1.97 ± 0.29 vs. 0.39 ± 0.73, P = .036). In advanced stages of tumor (stage III, IV), a significantly higher MRE of Twist1 (2.47 ± 0.41 vs. 1.25 ± 0.36, P = .035) and MAML1 (3.05 ± 0.45 vs. 1.07 ± 0.59, P = .021) mRNA was observed.

Conclusions

We introduce Twist1 and MAML1 as new molecular markers of advanced tumor, which determine the characteristics and aggressive behavior of ESCC. Along with the emerging evidence of their role in different cellular processes and aberrations in various cancers, they are suggested as potentially interesting therapeutic targets to reverse a broad spectrum of functional aberrations that promote ESCC development.

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Acknowledgment

The authors gratefully acknowledge the review of our manuscript by Mr. Danial Afsharzadeh. The authors are also thankful to Ezzat Dadkhah, Azadeh A’rabi, and Martha Ghahraman at the Division of Human Genetics for their technical assistance. Additionally, we appreciate all our colleagues at the departments of Surgery and Pathology at Omid Hospital for their help in gathering and preparing tissue specimens. This study was supported by a grant (No. 51423880299007) from Islamic Azad University, Damghan Branch, Damghan, Iran.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Mohammad Mahdi Forghanifard PhD, Taher Nejadsattari PhD & Kazem Parivar PhD

  2. Department of Biology, Damghan Branch, Islamic Azad University, Damghan, Iran

    Mohammad Mahdi Forghanifard PhD

  3. Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

    Omeed Moaven MD

  4. Human Genetic Division, Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Moein Farshchian MSc, Reza Raeisossadati MSc, Meysam Moghbeli MSc & Mohammad Reza Abbaszadegan PhD

  5. Department of Pathology, Omid Hospital, MUMS, Mashhad, Iran

    Mehdi Montazer MD

  6. Department of Surgery, Omid Hospital, MUMS, Mashhad, Iran

    Abbas Abdollahi MD

  7. Division of Human Genetics, Avicenna Research Institute, Mashhad University of Medical Sciences, Mashhad, 9196773117, Iran

    Mohammad Reza Abbaszadegan PhD

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  1. Mohammad Mahdi Forghanifard PhD
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  2. Omeed Moaven MD
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Correspondence to Mohammad Reza Abbaszadegan PhD.

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Forghanifard, M.M., Moaven, O., Farshchian, M. et al. Expression Analysis Elucidates the Roles of MAML1 and Twist1 in Esophageal Squamous Cell Carcinoma Aggressiveness and Metastasis. Ann Surg Oncol 19, 743–749 (2012). https://doi.org/10.1245/s10434-011-2074-8

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  • DOI: https://doi.org/10.1245/s10434-011-2074-8

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