Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival

Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clini...

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Main Authors: Kong, Yink Heay, Syed Zanaruddin, Sharifah Nurain, Lau, Shin Hin, Ramanathan, Anand, Kallarakkal, Thomas George, Vincent-Chong, Vui King, Wan Mustafa, Wan Mahadzir, Abraham, Mannil Thomas, Abdul Rahman, Zainal Ariff, Zain, Rosnah Binti, Cheong, Sok Ching
Format: Online
Language:English
Published: Public Library of Science 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516250/
id pubmed-4516250
recordtype oai_dc
spelling pubmed-45162502015-07-29 Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival Kong, Yink Heay Syed Zanaruddin, Sharifah Nurain Lau, Shin Hin Ramanathan, Anand Kallarakkal, Thomas George Vincent-Chong, Vui King Wan Mustafa, Wan Mahadzir Abraham, Mannil Thomas Abdul Rahman, Zainal Ariff Zain, Rosnah Binti Cheong, Sok Ching Research Article Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer’s aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT) is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1 and LAMC2) at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated with Broder’s grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management. Public Library of Science 2015-07-27 /pmc/articles/PMC4516250/ /pubmed/26214683 http://dx.doi.org/10.1371/journal.pone.0134045 Text en © 2015 Kong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Kong, Yink Heay
Syed Zanaruddin, Sharifah Nurain
Lau, Shin Hin
Ramanathan, Anand
Kallarakkal, Thomas George
Vincent-Chong, Vui King
Wan Mustafa, Wan Mahadzir
Abraham, Mannil Thomas
Abdul Rahman, Zainal Ariff
Zain, Rosnah Binti
Cheong, Sok Ching
spellingShingle Kong, Yink Heay
Syed Zanaruddin, Sharifah Nurain
Lau, Shin Hin
Ramanathan, Anand
Kallarakkal, Thomas George
Vincent-Chong, Vui King
Wan Mustafa, Wan Mahadzir
Abraham, Mannil Thomas
Abdul Rahman, Zainal Ariff
Zain, Rosnah Binti
Cheong, Sok Ching
Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival
author_facet Kong, Yink Heay
Syed Zanaruddin, Sharifah Nurain
Lau, Shin Hin
Ramanathan, Anand
Kallarakkal, Thomas George
Vincent-Chong, Vui King
Wan Mustafa, Wan Mahadzir
Abraham, Mannil Thomas
Abdul Rahman, Zainal Ariff
Zain, Rosnah Binti
Cheong, Sok Ching
author_sort Kong, Yink Heay
title Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival
title_short Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival
title_full Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival
title_fullStr Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival
title_full_unstemmed Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival
title_sort co-expression of twist1 and zeb2 in oral squamous cell carcinoma is associated with poor survival
description Oral squamous cell carcinoma (OSCC) is an aggressive disease accounting for more than 260,000 cancer cases diagnosed and 128,000 deaths worldwide. A large majority of cancer deaths result from cancers that have metastasized beyond the primary tumor. The relationship between genetic changes and clinical outcome can reflect the biological events that promote cancer’s aggressive behavior, and these can serve as molecular markers for improved patient management and survival. To this end, epithelial-mesenchymal transition (EMT) is a major process that promotes tumor invasion and metastasis, making EMT-related proteins attractive diagnostic biomarkers and therapeutic targets. In this study, we used immunohistochemistry to study the expression of a panel of transcription factors (TWIST1, SNAI1/2, ZEB1 and ZEB2) and other genes intimately related to EMT (CDH1 and LAMC2) at the invasive tumor front of OSCC tissues. The association between the expression of these proteins and clinico-pathological parameters were examined with Pearson Chi-square and correlation with survival was analyzed using Kaplan Meier analysis. Our results demonstrate that there was a significant differential expression of CDH1, LAMC2, SNAI1/2 and TWIST1 between OSCC and normal oral mucosa (NOM). Specifically, CDH1 loss was significantly associated with Broder’s grading, while diffused LAMC2 was similarly associated with non-cohesive pattern of invasion. Notably, co-expression of TWIST1 and ZEB2 in OSCC was significantly associated with poorer overall survival, particularly in patients without detectable lymph node metastasis. This study demonstrates that EMT-related proteins are differentially expressed in OSCC and that the co-expression of TWIST1 and ZEB2 could be of clinical value in identifying patients with poor survival for appropriate patient management.
publisher Public Library of Science
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4516250/
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