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三大洲宫颈鳞癌队列的综合分析揭示了具有预后意义的保守亚型。

Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.

机构信息

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

出版信息

Nat Commun. 2022 Oct 7;13(1):5818. doi: 10.1038/s41467-022-33544-x.

Abstract

Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the USA, Europe and Sub-Saharan Africa and identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 and C2 tumours can be driven by either of the two most common HPV types in cervical cancer (16 and 18) and while HPV16 and HPV18 are overrepresented among C1 and C2 tumours respectively, the prognostic difference between groups is not due to HPV type. C2 tumours, which comprise approximately 20% of CSCCs across these cohorts, display distinct genomic alterations, including loss or mutation of the STK11 tumour suppressor gene, increased expression of several immune checkpoint genes and differences in the tumour immune microenvironment that may explain the shorter survival associated with this group. In conclusion, we identify two therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

摘要

人乳头瘤病毒(HPV)相关宫颈癌是导致女性癌症死亡的主要原因。在这里,我们对 643 例宫颈鳞状细胞癌(CSCC,宫颈癌最常见的组织学变异型)进行了综合的多组学分析,这些 CSCC 代表了来自美国、欧洲和撒哈拉以南非洲的患者人群,并确定了两种具有不同预后的 CSCC 亚型(C1 和 C2)。C1 和 C2 肿瘤可以由宫颈癌中两种最常见的 HPV 类型(16 型和 18 型)中的任何一种驱动,虽然 HPV16 和 HPV18 在 C1 和 C2 肿瘤中分别过表达,但组间的预后差异并非由于 HPV 类型。C2 肿瘤约占这些队列中 CSCC 的 20%,表现出明显的基因组改变,包括 STK11 肿瘤抑制基因的缺失或突变、几个免疫检查点基因的表达增加以及肿瘤免疫微环境的差异,这些可能解释了与该组相关的较短生存时间。总之,我们在三个地理分布不同的队列中发现了两种具有相同特征的与治疗相关的 CSCC 亚型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab24/9547055/5faab79ae9c3/41467_2022_33544_Fig1_HTML.jpg

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