Budhwani Megha, Lukowski Samuel W, Porceddu Sandro V, Frazer Ian H, Chandra Janin
Diamantina Institute, Translational Research Institute, The University of Queensland, Woolloongabba, QLD, Australia.
Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia.
Front Cell Infect Microbiol. 2020 Jun 25;10:307. doi: 10.3389/fcimb.2020.00307. eCollection 2020.
Human papillomavirus (HPV) infection is associated with a range of malignancies that affect anogenital and oropharyngeal sites. α-HPVs dominantly infect basal epithelial cells of mucosal tissues, where they dysregulate cell division and local immunity. The cervix is one of the mucosal sites most susceptible to HPV infections. It consists of anatomically diverse regions, and the majority of cervical intraepithelial neoplasia and cancers arise within the cervical squamo-columnar junction where undifferentiated basal progenitor cells with stem cell properties are found. The cancer stem cell theory particularly associates tumorigenesis, invasion, dissemination, and metastasis with cancer cells exhibiting stem cell properties. In this perspective, we discuss evidence of a cervical cancer stem cell niche and explore the association of stemness related genes with 5-year survival using a publicly available transcriptomic dataset of a cervical cancer cohort. We report that poor prognosis in this cohort correlates with overexpression of a subset of stemness pathway genes, a majority of which regulate the central Focal Adhesion pathway, and are also found to be enriched in the HPV infection pathway. These observations support therapeutic targeting of stemness genes overexpressed by mucosal cells infected with high-risk HPVs.
人乳头瘤病毒（HPV）感染与一系列影响肛门生殖器和口咽部位的恶性肿瘤相关。α-HPV主要感染黏膜组织的基底上皮细胞，在这些细胞中它们会破坏细胞分裂和局部免疫。子宫颈是最易受HPV感染的黏膜部位之一。它由解剖结构多样的区域组成，大多数宫颈上皮内瘤变和癌症发生在宫颈鳞柱交界区，此处存在具有干细胞特性的未分化基底祖细胞。癌症干细胞理论特别将肿瘤发生、侵袭、播散和转移与具有干细胞特性的癌细胞联系起来。从这个角度出发，我们讨论宫颈癌干细胞龛的证据，并使用一个公开可用的宫颈癌队列转录组数据集探索干性相关基因与5年生存率的关联。我们报告称，该队列中的不良预后与干性通路基因子集的过表达相关，其中大多数基因调节中心黏着斑通路，并且还发现它们在HPV感染通路中富集。这些观察结果支持针对感染高危HPV的黏膜细胞中过表达的干性基因进行治疗靶向。
