A hybrid epithelial/mesenchymal state in head and neck cancer: A biomarker for survival with differential prognosis by self-reported race.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Med Pub Date : 2024-07-12 Epub Date: 2024-06-19 DOI:10.1016/j.medj.2024.05.014
Angela L Mazul, Thomas F Barrett, Graham Colditz, Anuraag S Parikh, Salma Ramadan, Jose P Zevallos, Jason T Rich, R Alex Harbison, Ryan S Jackson, Patrik Pipkorn, Paul Zolkind, Itay Tirosh, Sidharth V Puram
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引用次数: 0

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) is the 6th 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.

Methods: 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.

Findings: 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]).

Conclusion: 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.

Funding: 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.]).

头颈癌的上皮/间质混合状态:自我报告的种族预后不同的生存期生物标志物。
背景:头颈部鳞状细胞癌(HNSCC头颈部鳞状细胞癌(HNSCC)是导致癌症相关死亡的第六大原因,种族差异加大了治疗方面的挑战。尽管混合上皮/间质(E/M)状态与肿瘤进展之间的关系令人感兴趣,但目前还没有研究描述混合E/M状态在自我报告的种族队列中与头颈部癌症结果的临床相关性:鉴于混合E/M恶性细胞和癌症相关成纤维细胞之间的基因表达存在重叠,我们对癌症基因组图谱中口腔和喉鳞癌肿瘤的大量RNA测序数据进行了解卷积。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,我们对自我报告的美国黑人和白人的总生存率和无病生存率进行了生存分析:研究结果:混合 E/M 状态与头颈癌生存率的关系因自我报告的种族和族裔而异,非西班牙裔黑人患者的混合 E/M 状态与头颈癌生存率的关系更为密切。混合 E/M 评分高的黑人患者死亡或复发的风险更高(危险比 [HR]: 4.18 [95% 置信区间]):4.18[95%置信区间(CI):2.06,8.49]])高于混合 E/M 评分高的白人患者(HR:1.58 [95% CI:1.11,2.26]):我们的研究结果表明,社会结构、种族主义和遗传多样性之间存在着复杂的相互作用。我们恳请研究人员考虑造成差异的社会和生物学背景:A.L.M.获得了美国国家少数民族健康和健康差异研究所(K01MD013897 [主要研究者(PI),A.L.M.])的资助。S.V.P. 接受了美国国家牙科和颅面研究所(R01DE032865 [PI, S.V.P.] 和 R01DE032371 [PI, S.V.P.])的资助。
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来源期刊
Med
Med MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
17.70
自引率
0.60%
发文量
102
期刊介绍: Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.
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