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Abstract：
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：这项研究深入研究了口腔癌的复杂景观，在亚洲国家高发的全球关注。我们专注于口腔鳞状细胞癌（OSCC），主要由槟榔及其衍生物的消费驱动。OSCC通常起因于癌前病变,如口腔粘膜下纤维化(OSF)。在巴基斯坦,由于各种成瘾物质，OSCC在男性中普遍存在，包括无烟烟草和咀嚼材料。肿瘤抑制基因突变，如TP53和p21，在这种恶性肿瘤的发展中起关键作用。我们还探讨了TUSC3基因缺失在OSCC和OSF中的参与。
方法：在这项研究中，我们调查了人口统计学，TUSC3基因表达，删除分析,在有烟草衍生物使用史的OSCC和OSF患者（每种情况下50个样本的血液和组织）中，TP53和p21基因改变。关联分析主要通过基于PCR的基因分型进行。
结果：该研究的患者队列（OSCC和OSF）显示出13至65岁的广泛年龄范围（平均值=32.96岁）。这两种情况在男性中更为普遍，男女比例约为2.5:1。咀嚼习惯分析显示，OSF和OSCC患者使用gutka的频率很高。OSCC细胞系中的TUSC3表达分析表明显著下调。基因分型显示OSF病例中没有TUSC3缺失，但在OSCC组织样本中的缺失率超过22%。分析支持TUSC3缺失与OSCC发展显著相关，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。增加了他们的发病机制。我们的发现进一步揭示了TUSC3缺失与烟草和相关产品的过度使用之间的强相关性。揭示OSCC发育的遗传基础。
结论：值得注意的是，我们的研究为OSCC和OSF的遗传方面提供了重要的见解，以应对槟榔的成瘾性消费，槟榔,和烟草衍生物。TUSC3缺失和OSCC发展之间存在显著关联，TP53和p21的多态性强调了进一步研究驱动口腔癌进展的分子机制以改善诊断和治疗结果的重要性.
方法：在这项研究中，我们调查了人口统计学，TUSC3基因表达，删除分析,在有烟草衍生物使用史的OSCC和OSF患者（每种情况下50个样本的血液和组织）中，TP53和p21基因改变。关联分析主要通过基于PCR的基因分型进行。
结果：该研究的患者队列（OSCC和OSF）显示出13至65岁的广泛年龄范围（平均值=32.96岁）。这两种情况在男性中更为普遍，男女比例约为2.5:1。咀嚼习惯分析显示，OSF和OSCC患者使用gutka的频率很高。OSCC细胞系中的TUSC3表达分析表明显著下调。基因分型显示OSF病例中没有TUSC3缺失，但在OSCC组织样本中的缺失率超过22%。分析支持TUSC3缺失与OSCC发展显著相关，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。增加了他们的发病机制。我们的发现进一步揭示了TUSC3缺失与烟草和相关产品的过度使用之间的强相关性。揭示OSCC发育的遗传基础。
结论：值得注意的是，我们的研究为OSCC和OSF的遗传方面提供了重要的见解，以应对槟榔的成瘾性消费，槟榔,和烟草衍生物。TUSC3缺失和OSCC发展之间存在显著关联，TP53和p21的多态性强调了进一步研究驱动口腔癌进展的分子机制以改善诊断和治疗结果的重要性.
