Mazul Angela L, Barrett Thomas F, Colditz Graham, Parikh Anuraag S, Ramadan Salma, Zevallos Jose P, Rich Jason T, Harbison R Alex, Jackson Ryan S, Pipkorn Patrik, Zolkind Paul, Tirosh Itay, Puram Sidharth V
Department of Otolaryngology/Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; Division of Public Health Science, Department of Surgery, Washington University School of Medicine, St. Louis, MO, USA; Department of Otolaryngology/Head and Neck Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Otolaryngology/Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Med. 2024 Jul 12;5(7):826-831.e3. doi: 10.1016/j.medj.2024.05.014. Epub 2024 Jun 19.
Head and neck squamous cell carcinoma (HNSCC) is the 6 leading cause of cancer-related mortality, with racial disparities amplifying the challenges in treatment. Although the relationship between hybrid epithelial/mesenchymal (E/M) states and tumor progression is of interest, no studies have characterized the clinical relevance of hybrid E/M states in head and neck cancer outcomes among self-reported racial cohorts.
Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans.
The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported race and ethnicity, with a stronger association in non-Hispanic Black patients. Black patients with a high hybrid E/M score had a higher risk of death or recurrence (hazard ratio [HR]: 4.18 [95% confidence interval (CI): 2.06, 8.49]) than White patients with a high hybrid E/M score (HR: 1.58 [95% CI: 1.11, 2.26]).
Our results suggest a complex interplay of social structure, racism, and genetic diversity. We implore researchers to consider the social and biological context contributing to disparities.
A.L.M. received support from the National Institute of Minority Health and Health Disparities (K01MD013897 [principal investigator (PI), A.L.M.]). S.V.P. received support from the National Institute of Dental and Craniofacial Research (R01DE032865 [PI, S.V.P.] and R01DE032371 [PI, S.V.P.]).
头颈部鳞状细胞癌（HNSCC）是癌症相关死亡的第六大主要原因，种族差异加剧了治疗挑战。尽管混合上皮/间充质（E/M）状态与肿瘤进展之间的关系备受关注，但尚无研究描述自我报告种族队列中混合E/M状态在头颈癌预后中的临床相关性。
鉴于混合E/M恶性细胞与癌症相关成纤维细胞之间基因表达的重叠，我们利用来自癌症基因组图谱的口腔和喉鳞状细胞癌肿瘤的批量RNA测序数据进行反卷积分析。我们利用之前收集的单细胞图谱生成推断的恶性图谱，然后对这些图谱进行混合E/M评分。然后，我们对自我报告的黑人和白人美国人的总生存期和无病生存期进行了生存分析。
混合E/M状态与自我报告的种族和族裔的头颈癌生存期存在差异关联，在非西班牙裔黑人患者中关联更强。混合E/M评分高的黑人患者比混合E/M评分高的白人患者有更高的死亡或复发风险（风险比[HR]：4.18[95%置信区间（CI）：2.06，8.49]）（HR：1.58[95%CI：1.11，2.26]）。
我们的结果表明社会结构、种族主义和遗传多样性之间存在复杂的相互作用。我们恳请研究人员考虑导致差异的社会和生物学背景。
A.L.M.获得了国家少数族裔健康与健康差异研究所的支持（K01MD013897[主要研究者（PI），A.L.M.]）。S.V.P.获得了国家牙科和颅面研究所的支持（R01DE032865[PI，S.V.P.]和R01DE032371[PI，S.V.P.]）。
