目的:通过单细胞分子表征确定与循环肿瘤细胞(CTC)相关的头颈部鳞状细胞癌的信号通路失调。
背景:头颈部鳞状细胞癌(HNSCC)具有重大的全球负担,是一种生存率低的疾病。尽管试验探索了新的治疗方式来提高疾病控制率,5年生存率仍然很低,仅为60%。据报道,由于治疗抗性癌细胞产生的转移活性,大多数癌症恶性肿瘤进展到致命阶段。被认为是发展有效癌症治疗方案的最重要障碍之一。然而,癌细胞的分子特征尚未得到彻底研究。
方法:这里,我们检查了原位HNSCC肿瘤,并基于替代生物标志物对下游循环肿瘤细胞(CTC)进行了配对随访,以检测在其他癌症中确定的转移-尚未在HNSCC治疗算法中完全采用.
结果:具体来说,我们揭示了转移性HNSCC患者具有复杂的CTC,这些CTC可以通过基因表达和突变基因图谱进行定义,这些基因来自完整的单细胞RNASeq(scRNASeq),用于确认这些CTC固有的分子途径.为了提高我们研究结果的可靠性,我们与以前发表的研究结果交叉验证了这些分子谱.
结论:因此,我们在CTC中鉴定了5条失调的信号通路,以获得HNSCC生物标志物组,用于筛查HNSCC原位肿瘤.
目的使用单细胞分子表征研究与循环肿瘤细胞(CTC)相关的头颈部鳞状细胞癌(HNSCC)的信号通路失调。尽管在治疗方面取得了进步,但HNSCC带来了巨大的全球健康负担,存活率低。治疗抗性癌细胞的转移活性仍然是开发有效治疗的主要挑战。然而,癌细胞的分子特征,特别是CTC,不是很了解。方法我们使用替代生物标志物分析原位HNSCC肿瘤和相应的CTC,以检测转移,一种在HNSCC治疗方案中未广泛使用的技术。结果我们的研究揭示了转移性HNSCC患者的复杂CTC,其特征是通过单细胞RNASeq(scRNASeq)进行基因表达和突变基因谱分析。这些概况证实了CTC固有的分子途径,进一步验证了以往的研究。结论通过我们的研究,我们在CTC中发现了5个失调的信号通路,提示HNSCC原位肿瘤筛查的潜在生物标志物小组。
OBJECTIVE: To determine the dysregulated signaling pathways of head and neck squamous cell carcinoma associated with circulating tumor cells (CTCs) via single-cell molecular characterization.
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a significant global burden and is a disease with poor survival. Despite trials exploring new treatment modalities to improve disease control rates, the 5 year survival rate remains low at only 60%. Most cancer malignancies are reported to progress to a fatal phase due to the metastatic activity derived from treatment-resistant cancer cells, regarded as one of the most significant obstacles to develope effective cancer treatment options. However, the molecular profiles of cancer cells have not been thoroughly studied.
METHODS: Here, we examined in-situ HNSCC tumors and pairwisely followed up with the downstream circulating tumor cells (CTCs)-based on the surrogate biomarkers to detect metastasis that is established in other cancers - not yet being fully adopted in HNSCC treatment algorithms.
RESULTS: Specifically, we revealed metastatic HNSCC patients have complex CTCs that could be defined through gene expression and mutational gene profiling derived from completed single-cell RNASeq (scRNASeq) that served to confirm molecular pathways inherent in these CTCs. To enhance the reliability of our findings, we cross-validated those molecular profiles with results from previously published studies.
CONCLUSIONS: Thus, we identified 5 dysregulated signaling pathways in CTCs to derive HNSCC biomarker panels for screening HNSCC in situ tumors.
ObjectivesInvestigating the dysregulated signaling pathways of head and neck squamous cell carcinoma (HNSCC) linked with circulating tumor cells (CTCs) using single-cell molecular characterization.IntroductionHNSCC poses a significant global health burden with poor survival rates despite advancements in treatment. Metastatic activity from treatment-resistant cancer cells remains a major challenge in developing effective treatments. However, the molecular profiles of cancer cells, particularly CTCs, are not well-understood.MethodsWe analyzed in-situ HNSCC tumors and corresponding CTCs using surrogate biomarkers to detect metastasis, a technique not widely used in HNSCC treatment protocols.ResultsOur study revealed complex CTCs in metastatic HNSCC patients characterized by gene expression and mutational gene profiling via single-cell RNASeq (scRNASeq). These profiles confirmed molecular pathways inherent in CTCs, further validated by previous research.ConclusionThrough our research, we identified five dysregulated signaling pathways in CTCs, suggesting potential biomarker panels for HNSCC screening in situ tumors.