School of Public Health, Xinxiang Medical University, Xinxiang, Henan, China.
Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan, China.
PLoS One. 2022 Jun 3;17(6):e0269462. doi: 10.1371/journal.pone.0269462. eCollection 2022.
Hypoxia is a common microenvironment condition in most malignant tumors and has been shown to be associated with adverse outcomes of cervical cancer patients. In this study, we investigated the effects of hypoxia-related genes on tumor progress to characterize the tumor hypoxic microenvironment.
We retrieved a set of hypoxia-related genes from the Molecular Signatures Database and evaluated their prognostic value for cervical cancer. A hypoxia-based prognostic signature for cervical cancer was then developed and validated using tumor samples from two independent cohorts (TCGA-CESC and CGCI-HTMCP-CC cohorts). Finally, we validated the hypoxia prediction of ccHPS score in eight human cervical cancer cell lines treated with the hypoxic and normoxic conditions, and 286 tumor samples with hypoxic category (more or less) from Gene Expression Omnibus (GEO) database with accession GSE72723.
A risk signature model containing nine hypoxia-related genes was developed and validated in cervical cancer. Further analysis showed that this risk model could be an independent prognosis factor of cervical cancer, which reflects the condition of the hypoxic tumor microenvironment and its remodeling of cell metabolism and tumor immunity. Furthermore, a nomogram integrating the novel risk model and lymphovascular invasion status was developed, accurately predicting the 1-, 3- and 5-year prognosis with AUC values of 0.928, 0.916 and 0.831, respectively. These findings provided a better understanding of the hypoxic tumor microenvironment in cervical cancer and insights into potential new therapeutic strategies in improving cancer therapy.
缺氧是大多数恶性肿瘤常见的微环境条件，并已被证明与宫颈癌患者的不良结局相关。在这项研究中，我们研究了与缺氧相关的基因对肿瘤进展的影响，以描述肿瘤缺氧微环境。
我们从分子特征数据库中检索了一组与缺氧相关的基因，并评估了它们对宫颈癌的预后价值。然后使用来自两个独立队列（TCGA-CESC 和 CGCI-HTMCP-CC 队列）的肿瘤样本开发和验证了基于缺氧的宫颈癌预后签名。最后，我们验证了 ccHPS 评分在缺氧和常氧条件下处理的 8 个人宫颈癌细胞系以及 GEO 数据库中具有缺氧类别（更多或更少）的 286 个肿瘤样本中的缺氧预测，GEO 数据库 accession GSE72723。
开发并验证了包含九个与缺氧相关的基因的宫颈癌风险签名模型。进一步分析表明，该风险模型可以作为宫颈癌的独立预后因素，反映了缺氧肿瘤微环境及其重塑细胞代谢和肿瘤免疫的情况。此外，还开发了一个整合新风险模型和淋巴血管侵犯状态的列线图，能够准确预测 1、3 和 5 年的预后，AUC 值分别为 0.928、0.916 和 0.831。这些发现为宫颈癌缺氧肿瘤微环境提供了更好的理解，并为改善癌症治疗的潜在新治疗策略提供了思路。
