Sadeghirad Habib, Monkman James, Mehdi Ahmed M, Ladwa Rahul, O'Byrne Ken, Hughes Brett G M, Kulasinghe Arutha
The University of Queensland Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Queensland Cyber Infrastructure Foundation Ltd., QCIF Facility for Advanced Bioinformatics, Brisbane, QLD, Australia.
Front Immunol. 2022 May 16;13:895513. doi: 10.3389/fimmu.2022.895513. eCollection 2022.
Head and neck squamous cell carcinoma (HNSCC) often presents 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 their efficacy at controlling occult distant sites remains poor. While our understanding of the tumor microenvironment conducive to 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 tumors, and stromal compartments of the respective sites in samples of both matched and unmatched patients. In unmatched analyses of n = 43 primary and 11 nodal metastases, our data indicated that tumor 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 tumors. Univariate, overall survival (OS) analysis indicated CD25 in tumor regions of primary tumors to be associated with reduced survival (HR = 3.3, p = 0.003), while progesterone receptor (PR) was associated with an improved OS (HR = 0.33, p = 0.015). This study highlights the utility of spatial proteomics for delineating the tumor and stromal compartment composition, and utility toward understanding these properties in locoregional metastasis. These findings indicate unique biological properties of lymph node metastases that may elucidate further understanding of distant metastatic in OPSCC.
头颈部鳞状细胞癌（HNSCC）尽管采用了多模式治疗方法，包括手术切除、放化疗，以及最近用于转移性或复发性HNSCC的免疫治疗，但仍常出现局部区域或远处疾病。治疗通常针对原发性和淋巴结区域的HNSCC部位，而它们在控制隐匿性远处部位方面的疗效仍然很差。虽然我们对有利于有效治疗的肿瘤微环境的理解在不断增加，但局部区域部位的生物学基础仍不清楚。在这里，我们对头颈部鳞状细胞癌（OPSCC）队列中的原发性肿瘤和淋巴结转移灶应用靶向空间蛋白质组学方法，以了解肿瘤内蛋白质的表达，以及匹配和不匹配患者样本中各部位的基质区室。在对43例原发性肿瘤和11例淋巴结转移灶的非匹配分析中，我们的数据表明，淋巴结转移灶中的肿瘤细胞具有较高水平的Ki-67、PARP、BAD和裂解的半胱天冬酶9，这表明这些转移细胞内的增殖、DNA修复和凋亡增加。相反，在匹配分析（n = 7）中，促凋亡标志物BIM和BAD在原发性肿瘤的基质中富集。单变量总体生存（OS）分析表明，原发性肿瘤肿瘤区域中的CD25与生存率降低相关（HR = 3.3，p = 0.003），而孕激素受体（PR）与OS改善相关（HR = 0.33，p = 0.015）。本研究强调了空间蛋白质组学在描绘肿瘤和基质区室组成方面的实用性，以及在理解局部区域转移中的这些特性方面的实用性。这些发现表明了淋巴结转移的独特生物学特性，这可能有助于进一步了解口咽鳞状细胞癌中的远处转移。
