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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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/ |
_version_ |
1613252637159849984 |