Stucky Andres, Viet Chi T, Aouizerat Bradley E, Ye Yi, Doan Coleen, Mundluru Tarun, Sedhiazadeh Parish, Sinha Uttam K, Chen Xuelian, Zhang Xi, Li Shengwen Calvin, Cai Jin, Zhong Jiang F
Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, CA, USA.
Department of Oral and Maxillofacial Surgery, School of Dentistry, Loma Linda University, Loma Linda, CA, USA.
Cancer Control. 2024 Jan-Dec;31:10732748241251571. doi: 10.1177/10732748241251571.
To determine the dysregulated signaling pathways of head and neck squamous cell carcinoma associated with circulating tumor cells (CTCs) via single-cell molecular characterization.
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.
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.
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.
Thus, we identified 5 dysregulated signaling pathways in CTCs to derive HNSCC biomarker panels for screening HNSCC in situ tumors.
通过单细胞分子特征分析确定头颈部鳞状细胞癌与循环肿瘤细胞（CTC）相关的失调信号通路。
头颈部鳞状细胞癌（HNSCC）在全球负担沉重，是一种生存率低的疾病。尽管有试验探索新的治疗方式以提高疾病控制率，但5年生存率仍仅为60%，处于较低水平。据报道，大多数癌症恶性肿瘤由于源自耐药癌细胞的转移活性而进展到致命阶段，这被认为是开发有效癌症治疗方案的最大障碍之一。然而，癌细胞的分子特征尚未得到充分研究。
在此，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）进行配对随访，以检测转移情况，这种方法在其他癌症中已确立，但尚未完全应用于HNSCC治疗方案。
具体而言，我们发现转移性HNSCC患者具有复杂的CTC，可通过来自完整单细胞RNA测序（scRNASeq）的基因表达和突变基因谱来定义，这有助于确认这些CTC中固有的分子途径。为提高我们研究结果的可靠性，我们将这些分子谱与先前发表的研究结果进行了交叉验证。
因此，我们在CTC中鉴定出5条失调的信号通路，以推导用于筛查原位HNSCC肿瘤的HNSCC生物标志物组。
