Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.
Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.
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对来自三大洲的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。
DOI：
10.1038/s41467-022-33544-x
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发表时间：
2022-10-07
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
人类乳头瘤病毒(HPV)相关的宫颈癌是女性癌症死亡的主要原因。在这里，我们对643例宫颈鳞癌(CSCC，宫颈癌最常见的组织学变体)进行了综合的多组学分析，代表了来自美国、欧洲和撒哈拉以南非洲的患者群体，并确定了两种预后不同的CSCC亚型(C1和C2)。宫颈癌中最常见的两种HPV类型(16和18)中的任何一种都可能导致C1和C2肿瘤的发生，虽然HPV16和HPV18在C1和C2肿瘤中分别过度表达，但两组之间的预后差异并不是由于HPV型。C2肿瘤约占这些队列中CSCC的20%，表现出明显的基因组变化，包括STK11肿瘤抑制基因的丢失或突变，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，这可能是与这一组相关的较短生存期的原因。总而言之，我们确定了两种与治疗相关的CSCC亚型，它们在三个地理位置不同的队列中具有相同的定义特征。人乳头瘤病毒(HPV)是宫颈癌的已知病因。在这里，作者使用来自美国、欧洲和撒哈拉以南非洲的已发表的宫颈鳞癌队列进行了多组学分析，并确定了两种显示预后差异的宫颈鳞癌亚型。
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. Human papillomavirus (HPV) is a known cause of cervical cancer. Here, the authors perform a multi-omic analysis using published cervical squamous cell carcinoma cohorts from the USA, Europe, and SubSaharan Africa and identify two cervical squamous cell carcinoma subtypes that display prognostic differences.
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