Title:Expression Profiling of EMT Transcriptional Regulators ZEB1 and ZEB2
in Different Histopathological Grades of Oral Squamous Cell Carcinoma
Patients
Volume: 25
Issue: 2
Author(s): Neha Baqai, Rafat Amin*, Tehseen Fatima, Zeba Ahmed and Nousheen Faiz
Affiliation:
- Dow College of Biotechnology, Dow University of Health Sciences, Ojha Campus, Karachi, Pakistan
Keywords:
Epithelial-mesenchymal transition, moderately differentiated squamous cell carcinoma, oral squamous cell carcinoma, poorly differentiated squamous cell carcinoma, well differentiated squamous cell carcinoma, zinc finger E-box.
Abstract:
Background: Pakistan has a high burden of oral cancers, with a prevalence rate of
around 9%. Oral Squamous Cell Carcinoma (OSCC) accounts for about 90% of oral cancer cases.
Epithelial to Mesenchymal Transition (EMT) gets highly stimulated in tumor cells by adopting
subsequent malignant features of highly invasive cancer populations. Zinc Finger E-Box binding
factors, ZEB1 and ZEB2, are regulatory proteins that promote EMT by suppressing the adherent
ability of cells transforming into highly motile cancerous cells. The present study aimed to analyze
the expression of EMT regulators, ZEB1 and ZEB2, and their association with the clinicopathological
features in different grades of OSCC patients.
Methods: Tissue samples were collected for both case and control groups from the recruited study
participants. Cancer tissues (cases) were collected from the confirmed OSCC patients, and healthy
tissues (controls) were collected from third-molar dental extraction patients. The study participants
were recruited with informed consent and brief demographic and clinical characteristics.
The case group was further segregated with respect to the histological cancer grading system into
well-differentiated (WD), moderately differentiated (MD), and poorly differentiated (PD) squamous
cell carcinoma (SCC) groups. RNA was extracted from the tissue samples for expression
profiling of ZEB1 and ZEB2 genes through quantitative real-time PCR (qRT-PCR).
Results: All of the recruited participants had a mean age of 46.55 ± 11.7 (years), with most of
them belonging to Urdu speaking ethnic group and were married. The BMI (kg/m2) of the healthy
participants was in the normal range (18-22 kg/m2). However, BMI was found to be reduced with
the proliferation in the pathological state of cancer. The oral hygiene of patients was better than
the healthy participants, possibly due to the strict oral hygiene practice concerns of consultants.
Every recruited OSCC patient had one or multiple addiction habits for more than a year. Patients
reported health frailty (46.6%), unhealed mouth sores (40%), swallowing difficulties and
white/reddish marks (80%), and restricted mouth opening (64.4%). Furthermore, 82.2% of the recruited
patients observed symptoms within 1-12 months, and buccal mucosa was the most exposed
tumor site among 55.6% of the patients. Expression profiling of EMT regulators showed
gradual over-expressions of ZEB1 (8, 20, and 42 folds) and ZEB2 (4, 10, and 18 folds) in respective
histological cancer grades.
Conclusion: High expressions of ZEBs have been significantly associated with cancer progression
and poor health. However, no association was found between OSCC with other clinicopathological
features when compared to healthy controls.
