title: Co-Expression of TWIST1 and ZEB2 in Oral Squamous Cell Carcinoma Is Associated with Poor Survival.
abstract: 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.
authors.affiliation: Department of Oro-maxillofacial Surgery and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research Team, Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.
authors.forename: Yink Heay
authors.initials: YH
authors.lastname: Kong
authors.affiliation: Oral Cancer Research Team, Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.
authors.forename: Sharifah Nurain
authors.initials: SN
authors.lastname: Syed Zanaruddin
authors.affiliation: Stomatology Unit, Institute for Medical Research, Kuala Lumpur, Malaysia.
authors.forename: Shin Hin
authors.initials: SH
authors.lastname: Lau
authors.affiliation: Department of Oro-maxillofacial Surgery and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research & Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Anand
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Department of Oro-maxillofacial Surgery and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research & Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Thomas George
authors.initials: TG
authors.lastname: Kallarakkal
authors.affiliation: Oral Cancer Research & Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Vui King
authors.initials: VK
authors.lastname: Vincent-Chong
authors.affiliation: Department of Oral & Maxillofacial Surgery, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Wan Mahadzir
authors.initials: WM
authors.lastname: Wan Mustafa
authors.affiliation: Department of Oral & Maxillofacial Surgery, Tengku Ampuan Rahimah Hospital, Klang, Malaysia.
authors.forename: Mannil Thomas
authors.initials: MT
authors.lastname: Abraham
authors.affiliation: Department of Oro-maxillofacial Surgery and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research & Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Zainal Ariff
authors.initials: ZA
authors.lastname: Abdul Rahman
authors.affiliation: Department of Oro-maxillofacial Surgery and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research & Coordinating Centre, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Rosnah Binti
authors.initials: RB
authors.lastname: Zain
authors.affiliation: Department of Oro-maxillofacial Surgery and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia; Oral Cancer Research Team, Cancer Research Initiatives Foundation, Subang Jaya, Selangor, Malaysia.
authors.forename: Sok Ching
authors.initials: SC
authors.lastname: Cheong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000096:biosynthesis*; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009687:Nuclear Proteins / Q000096:biosynthesis*; D012097:Repressor Proteins / Q000096:biosynthesis*; D015996:Survival Rate; D051879:Twist-Related Protein 1 / Q000096:biosynthesis*; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2