Baqai Neha, Amin Rafat, Fatima Tehseen, Ahmed Zeba, Faiz Nousheen
Dow Research Institute of Biotechnology and Biomedical Sciences, Dow University of Health Sciences, Ojha Campus, Karachi, Pakistan.
Dow College of Biotechnology, Dow University of Health Sciences, Ojha Campus, Karachi, Pakistan.
Curr Genomics. 2024 Apr 8;25(2):140-151. doi: 10.2174/0113892029284920240212091903.
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.
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).
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/m) of the healthy participants was in the normal range (18-22 kg/m). 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.
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.
巴基斯坦口腔癌负担沉重，患病率约为9%。口腔鳞状细胞癌（OSCC）约占口腔癌病例的90%。上皮-间质转化（EMT）在肿瘤细胞中通过呈现高侵袭性癌群体的后续恶性特征而受到高度刺激。锌指E盒结合因子ZEB1和ZEB2是调节蛋白，通过抑制细胞转化为高迁移性癌细胞的黏附能力来促进EMT。本研究旨在分析EMT调节因子ZEB1和ZEB2的表达及其与不同分级OSCC患者临床病理特征的关联。
从招募的研究参与者中收集病例组和对照组的组织样本。癌组织（病例组）取自确诊的OSCC患者，健康组织（对照组）取自拔除第三磨牙的患者。研究参与者在获得知情同意后被招募，并记录简要的人口统计学和临床特征。病例组根据组织学癌症分级系统进一步分为高分化（WD）、中分化（MD）和低分化（PD）鳞状细胞癌（SCC）组。从组织样本中提取RNA，通过定量实时PCR（qRT-PCR）对ZEB1和ZEB2基因进行表达谱分析。
所有招募的参与者平均年龄为46.55±11.7岁，他们大多属于说乌尔都语的族群且已婚。健康参与者的体重指数（kg/m）在正常范围内（18 - 22 kg/m）。然而，发现随着癌症病理状态的发展体重指数降低。患者的口腔卫生状况优于健康参与者，这可能是由于顾问对严格口腔卫生习惯的关注。每位招募的OSCC患者都有一种或多种超过一年的成瘾习惯。患者报告有身体虚弱（46.6%）、口腔溃疡未愈合（40%）、吞咽困难和白色/红色斑点（80%）以及张口受限（64.4%）。此外，82.2%的招募患者在1 - 12个月内出现症状，55.6%的患者中颊黏膜是最易出现肿瘤的部位。EMT调节因子的表达谱显示，在各自的组织学癌症分级中，ZEB1（8倍、20倍和42倍）和ZEB2（4倍、10倍和18倍）逐渐过度表达。
ZEBs的高表达与癌症进展和健康状况不佳显著相关。然而，与健康对照组相比未发现OSCC与其他临床病理特征之间存在关联。
