Ndiaye Moussa, Diop Gora, Derbois Celine, Spadoni Jean-Louis, Noirel Josselin, Medina-Santos Raissa, Coulonges Cedric, Torres Magali, Dieye Alioune, Sembene Mbacke, Deleuze Jean-François, Toledano Alain, Dem Ahmadou, Zagury Jean-François, Le Clerc Sigrid
Department of Animal Biology, Sciences and Techniques Faculty, Cheikh Anta DIOP University, 10700 Dakar, Senegal.
National Research Center for Human Genetics (CNRGH), Genomics Institute‑CEA, 91057 Evry, France.
Oncol Rep. 2023 Jun;49(6). doi: 10.3892/or.2023.8555. Epub 2023 Apr 28.
Cervical cancer (CC) is a multifactorial disease of which human papillomavirus (HPV) is the main etiological agent. Despite cervical Pap smear screening and anti‑HPV vaccination, CC remains a major public health issue. Identification of specific gene expression signatures in the blood could allow better insight into the immune response of CC and could provide valuable information for the development of novel biomarkers. The present study performed a transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from Senegalese patients with CC (n=31), low‑grade cervical intraepithelial neoplasia (CIN1; n=27) and from healthy control (CTR) subjects (n=29). Individuals in the CIN1 and CTR groups exhibited similar patterns in gene expression. A total of 182 genes were revealed to be differentially expressed in patients with CC compared with individuals in the CIN1 and CTR groups. The and genes were the most upregulated, whereas the T‑cell receptor α gene was the most downregulated in the CC group compared with in the CIN1 and CTR groups. The pathway enrichment analysis of the differentially expressed genes revealed pathways directly and indirectly linked to inflammation. To the best of our knowledge, the present study is the first large transcriptomic study on CC performed using PBMCs from African women; the results revealed the involvement of genes and pathways related to inflammation, most notably the IL‑1 pathway, and the involvement of downregulation of the T‑cell receptor α, a key component of the immune response. Several of the stated genes have already been reported in other cancer studies as putative blood biomarkers, thus reinforcing the requirement for deeper investigation. These findings may aid in the development of innovative clinical biomarkers for CC prevention and should be further replicated in other populations.
宫颈癌(CC)是一种多因素疾病,人乳头瘤病毒(HPV)是其主要病因。尽管有宫颈巴氏涂片筛查和抗HPV疫苗接种,宫颈癌仍然是一个重大的公共卫生问题。识别血液中特定的基因表达特征可以更好地了解宫颈癌的免疫反应,并可为新型生物标志物的开发提供有价值的信息。本研究对来自塞内加尔宫颈癌患者(n = 31)、低度宫颈上皮内瘤变(CIN1;n = 27)患者及健康对照(CTR)受试者(n = 29)的外周血单个核细胞(PBMC)进行了转录组分析。CIN1组和CTR组个体的基因表达模式相似。与CIN1组和CTR组个体相比,共发现182个基因在宫颈癌患者中差异表达。CC组中 和 基因上调最为明显,而与CIN1组和CTR组相比,T细胞受体α基因 下调最为明显。对差异表达基因的通路富集分析揭示了与炎症直接和间接相关的通路。据我们所知,本研究是首次使用非洲女性的PBMC对宫颈癌进行的大型转录组研究;结果揭示了与炎症相关的基因和通路的参与,最显著的是IL-1通路,以及免疫反应的关键组成部分T细胞受体α的下调。其他癌症研究中已将上述几个基因报道为假定的血液生物标志物,从而加强了深入研究的必要性。这些发现可能有助于开发用于宫颈癌预防的创新临床生物标志物,并且应该在其他人群中进一步验证。