Haghzad Tahereh, Khorsand Babak, Razavi S Adeleh, Hedayati Mehdi
Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran.
Department of Neurology, University of California, Irvine, CA, USA.
Endocrine. 2024 Nov;86(2):707-722. doi: 10.1007/s12020-024-03911-3. Epub 2024 Jun 17.
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, posing a growing clinical challenge. PTC exhibits two age-related peaks, with established risk factors including family history and radiation exposure. Managing even low-risk, localized PTC cases remain complex, with growing interest in active surveillance as an alternative to immediate surgery. This study employed single-cell RNA sequencing (scRNA-Seq) to explore the predictive value of BRAF and RAS mutations in PTC, shedding light on their impact on disease progression and outcomes. The analyses emphasized the significance of BRAF and RAS mutations in tumor advancement, particularly the unique BRAF V600E mutation associated with aggressive features. The methodology involved scRNA-Seq analysis of PTC and normal samples, unveiling distinct cell clusters and indicating upregulated BRAF and RAS genes. Pathway enrichment analysis highlighted altered biological processes and immune-related pathways in PTC. The study consolidated previous research showing the prevalence of BRAF and RAS mutations in PTC, subtypes with distinct molecular profiles, and the impact of TERT promoter mutations on disease severity. In summary, this study unveils the complex interplay of genetic mutations and the cellular microenvironment in PTC through scRNA-Seq. The upregulated BRAF and RAS genes suggest their roles as PTC drivers, and pathway enrichment reveals alterations in immune-related processes. This synthesis of prior research enhances our understanding of PTC's molecular foundations, informing better prognosis and personalized treatment approaches. These insights advance the landscape of PTC management and provide directions for further research.
乳头状甲状腺癌(PTC)是最常见的甲状腺癌,带来了日益严峻的临床挑战。PTC呈现出两个与年龄相关的发病高峰,已知的风险因素包括家族史和辐射暴露。即使是低风险、局限性的PTC病例,其管理仍然复杂,人们对主动监测作为立即手术的替代方案的兴趣与日俱增。本研究采用单细胞RNA测序(scRNA-Seq)来探索BRAF和RAS突变在PTC中的预测价值,阐明它们对疾病进展和预后的影响。分析强调了BRAF和RAS突变在肿瘤进展中的重要性,特别是与侵袭性特征相关的独特BRAF V600E突变。该方法涉及对PTC和正常样本进行scRNA-Seq分析,揭示了不同的细胞簇,并表明BRAF和RAS基因上调。通路富集分析突出了PTC中改变的生物学过程和免疫相关通路。该研究整合了先前的研究,显示了BRAF和RAS突变在PTC中的患病率、具有不同分子特征的亚型以及TERT启动子突变对疾病严重程度的影响。总之,本研究通过scRNA-Seq揭示了PTC中基因突变与细胞微环境之间的复杂相互作用。BRAF和RAS基因上调表明它们作为PTC驱动因素的作用,通路富集揭示了免疫相关过程的改变。对先前研究的综合增强了我们对PTC分子基础的理解,为更好的预后和个性化治疗方法提供了依据。这些见解推动了PTC管理的发展,并为进一步研究指明了方向。