小柯机器人

以色列魏兹曼研究所Itay Tirosh等研究人员合作发现，细胞状态与HPV相关口咽癌的基因组和病毒异质性相耦合。2023年4月3日，《自然—遗传学》杂志在线发表了这项成果。

研究人员使用单细胞RNA-seq来描述了人乳头瘤病毒（HPV）阳性和HPV阴性的口咽部肿瘤，并发现了肿瘤内和肿瘤之间高度的细胞多样性。首先，研究人员在单个肿瘤内检测到不同的染色体畸变，表明基因组不稳定，甚至在病理上阴性的边缘也能识别出恶性细胞。第二，研究人员发现了头颈部鳞状细胞癌（HNSCC）亚型和其他细胞状态的多样性，如细胞周期、衰老和上皮-间质转化。第三，研究人员发现HPV阳性肿瘤内病毒基因表达的异质性。HPV的表达在一部分细胞中消失或被抑制，这与HPV相关的细胞周期表型减少、对治疗的反应降低、侵袭增加和预后不佳有关。

这些发现表明，在诊断和治疗HPV阳性肿瘤时必须考虑HPV表达的多样性，这对预后有重要影响。

据介绍，HNSCC包括一个由HPV驱动的癌症亚群。

附：英文原文

Title: Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma

Author: Puram, Sidharth V., Mints, Michael, Pal, Ananya, Qi, Zongtai, Reeb, Ashley, Gelev, Kyla, Barrett, Thomas F., Gerndt, Sophie, Liu, Ping, Parikh, Anuraag S., Ramadan, Salma, Law, Travis, Mroz, Edmund A., Rocco, James W., Adkins, Doug, Thorstad, Wade L., Gay, Hiram A., Ding, Li, Paniello, Randal C., Pipkorn, Patrik, Jackson, Ryan S., Wang, Xiaowei, Mazul, Angela, Chernock, Rebecca, Zevallos, Jose P., Silva-Fisher, Jessica, Tirosh, Itay

Issue&Volume: 2023-04-03

Abstract: Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

DOI: 10.1038/s41588-023-01357-3

Source: https://www.nature.com/articles/s41588-023-01357-3

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex