Dissecting tissue compartment-specific protein signatures in primary and metastatic oropharyngeal squamous cell carcinomas. Dissecting tissue compartment-specific protein signatures in primary and metastatic oropharyngeal squamous cell carcinomas

Head and neck squamous cell carcinoma (HNSCC) often present with locoregional or distant disease, despite multimodal therapeutic approaches, which include surgical resection, chemoradiotherapy, and more recently immunotherapy for metastatic, or recurrent HNSCC. Therapies often target the primary and nodal regional HNSCC sites, and efficacy at controlling occult distant sites remains poor. Whilst our understanding of the tumour microenvironment, conducive for effective therapies is increasing, the biology underpinning locoregional sites remains unclear. Here, we applied targeted spatial proteomic approaches to primary and lymph node metastasis from an oropharyngeal SCC (OPSCC) cohort, to understand the expression of proteins within tumour, and stromal compartments of the respective sites in both matched and unmatched patients’ samples. In unmatched analyses of n=43 primary and 11 nodal metastasis, our data indicated that tumour cells in nodal metastases had higher levels of Ki-67, PARP, BAD and cleaved caspase 9, suggesting a role for increased proliferation, DNA repair and apoptosis within these metastatic cells. Conversely, in matched analyses (n=7), pro-apoptotic markers BIM and BAD were enriched in the stroma of primary tumours. Univariate, overall survival (OS) analysis indicated CD25 in tumour regions of primary tumours to be associated with reduced survival (HR=3.3, p=0.003), while partial response (PR) was associated with an improved OS (HR=0.33, p=0.015). This study highlights the utility of spatial proteomics for delineating tumour and stroma compartment composition, and the utility towards understanding these properties in locoregional metastasis. These findings indicate the unique biological properties of lymph node metastases that may elucidate further understanding of the subsequent distant metastatic potential of OPSCC. In this dataset, we applied GeoMx DSP protein profiling to tumour and tumour microenvironment regions of primary and lymphnode metastasis FFPE samples. The files here represent the Ncounter readout from this assay. Overall design: This dataset contains protein expression of tumour and tumour microenvironment regions from 43 primary tumours, 11 nodal metastases, with 7 additional patient matched primary/metastases

头颈部鳞状细胞癌（Head and neck squamous cell carcinoma, HNSCC）即便采用包括手术切除、放化疗以及近年用于转移性或复发性HNSCC的免疫疗法在内的多模式治疗策略，仍常出现局部区域或远处转移。现有治疗多针对原发灶及区域淋巴结病灶，而对隐匿性远处病灶的控制效果始终欠佳。尽管学界对助力有效治疗的肿瘤微环境的认知不断加深，但局部区域病灶背后的生物学机制仍不明晰。
本研究针对口咽鳞状细胞癌（oropharyngeal SCC, OPSCC）队列的原发灶与淋巴结转移灶，采用靶向空间蛋白质组学方法，旨在探究配对与非配对患者样本中，肿瘤及间质区域内的蛋白表达特征。在针对43例原发灶与11例淋巴结转移灶的非配对分析中，数据显示淋巴结转移灶内的肿瘤细胞Ki-67、PARP、BAD及裂解型半胱氨酸蛋白酶9（cleaved caspase 9）表达水平更高，提示这些转移瘤细胞的增殖、DNA修复及凋亡通路活性增强。与之相反，在7例配对样本分析中，促凋亡标志物BIM与BAD在原发灶间质中富集。
单变量总生存期（overall survival, OS）分析显示，原发灶肿瘤区域的CD25表达与不良预后相关（风险比=3.3，p=0.003），而部分缓解（partial response, PR）则与更佳的总生存期相关（风险比=0.33，p=0.015）。本研究证实了空间蛋白质组学在解析肿瘤与间质区域组成方面的应用价值，以及其在理解局部区域转移生物学特性中的潜力。上述发现揭示了淋巴结转移灶独特的生物学特性，或有助于进一步阐明OPSCC后续远处转移的潜在机制。
本数据集采用GeoMx DSP蛋白质谱技术，对原发灶及淋巴结转移灶的福尔马林固定石蜡包埋（Formalin-Fixed Paraffin-Embedded, FFPE）样本的肿瘤区域与肿瘤微环境区域进行检测。本批次文件对应该实验的Ncounter读数结果。实验整体设计：本数据集包含43例原发灶、11例淋巴结转移灶的肿瘤区域及肿瘤微环境区域的蛋白表达数据，其中包含7例配对的原发灶/转移灶患者样本。