The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi, Pakistan.
Shenzhen Key Laboratory of Anti-Aging and Regenerative Medicine, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518060, China.
BMC Oral Health. 2024 Jul 11;24(1):780. doi: 10.1186/s12903-024-04501-5.
This study delves into the intricate landscape of oral cancer, a global concern with a high incidence in Asian countries. We focus on oral squamous cell carcinoma (OSCC), primarily driven by the consumption of betel nut and its derivatives. OSCC often arises from premalignant lesions like oral submucous fibrosis (OSF). In Pakistan, OSCC is prevalent among men due to various addictive substances, including smokeless tobacco and chewing materials. Mutations in tumor suppressor genes, such as TP53 and p21, play crucial roles in this malignancy's development. We also explore the involvement of TUSC3 gene deletion in OSCC and OSF.
In this study we investigated demographics, TUSC3 gene expression, deletion analysis, and TP53 and p21 genetic alterations in OSCC and OSF patients (blood and tissue of 50 samples in each condition) who had tobacco derivates usage history. The association analysis was carried out mainly through PCR based genotyping.
The study's patient cohort (OSCC and OSF) displayed a wide age range from 13 to 65 years (Mean = 32.96 years). Both conditions were more prevalent in males, with a male-female ratio of approximately 2.5:1. Chewing habits analysis revealed high frequencies of gutka use in both OSF and OSCC patients. TUSC3 expression analysis in OSCC cell lines indicated significant downregulation. Genotyping showed no TUSC3 deletion in OSF cases, but a deletion rate of over 22% in OSCC tissue samples. Analysis supported a significant association of TUSC3 deletion with OSCC development but not with OSF. Polymorphism in p53 exon 4 and p21 (rs1801270) were significantly associated with both OSCC and OSF, adding to their pathogenesis. Our findings further revealed a strong correlation between TUSC3 deletion and the excessive use of tobacco and related products, shedding light on the genetic underpinnings of OSCC development.
Notably, our study provides a crucial insight into genetic aspects underlying OSCC and OSF in response of addictive consumption of areca nut, betel quid, and tobacco derivatives. A significant association between TUSC3 deletion and OSCC development, along with polymorphisms in TP53 and p21, underscores the importance of further research into the molecular mechanisms driving oral cancer progression for improved diagnosis and treatment outcomes.
本研究深入探讨了口腔癌这一全球性问题，亚洲国家的口腔癌发病率较高。我们重点研究口腔鳞状细胞癌（OSCC），其主要由槟榔及其衍生物的消费引起。OSCC 通常源自口腔黏膜下纤维性变（OSF）等癌前病变。在巴基斯坦，由于各种成瘾物质的存在，如无烟烟草和咀嚼物，男性中 OSCC 更为普遍。肿瘤抑制基因 TP53 和 p21 的突变在这种恶性肿瘤的发展中起着关键作用。我们还探讨了 TUSC3 基因缺失在 OSCC 和 OSF 中的作用。
本研究中，我们对有烟草衍生物使用史的 OSCC 和 OSF 患者（每组各 50 例患者的血液和组织样本）进行了人口统计学、TUSC3 基因表达、缺失分析以及 TP53 和 p21 遗传改变的研究。主要通过基于 PCR 的基因分型进行关联分析。
研究患者队列（OSCC 和 OSF）的年龄范围从 13 岁到 65 岁（平均年龄为 32.96 岁）。两种疾病在男性中更为普遍，男女比例约为 2.5:1。咀嚼习惯分析显示，OSF 和 OSCC 患者中均有较高的 Gutka 使用频率。OSCC 细胞系中的 TUSC3 表达分析表明其显著下调。基因分型显示 OSF 病例中没有 TUSC3 缺失，但在 OSCC 组织样本中缺失率超过 22%。分析表明，TUSC3 缺失与 OSCC 发生显著相关，但与 OSF 无关。p53 外显子 4 和 p21（rs1801270）的多态性与 OSCC 和 OSF 均显著相关，这增加了它们的发病机制。我们的研究结果进一步揭示了 TUSC3 缺失与烟草和相关产品过度使用之间的强烈相关性，为 OSCC 发生的遗传基础提供了新的认识。
值得注意的是，本研究深入探讨了槟榔、烟草及其衍生物成瘾性消费对 OSCC 和 OSF 的遗传基础，发现 TUSC3 缺失与 OSCC 发生之间存在显著关联，同时 TP53 和 p21 多态性也与 OSCC 和 OSF 显著相关。这突显了进一步研究口腔癌进展分子机制的重要性，以改善诊断和治疗结果。
