Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241288687. doi: 10.1177/15330338241288687.
Pancreatic cancer presents a formidable challenge with its aggressive nature and dismal prognosis, often hampered by elusive early symptoms. The tumor microenvironment (TME) emerges as a pivotal player in pancreatic cancer progression and treatment responses, characterized notably by hypoxia and immunosuppression. In this study, we aimed to identify hypoxia-related genes and develop a prognostic model for pancreatic cancer leveraging these genes.
Through analysis of gene expression data from The Cancer Genome Atlas (TCGA) and subsequent GO/KEGG enrichment analysis, hypoxia-related pathways were identified. We constructed a prognostic model using lasso regression and validated it using an independent dataset.
Our results showed that expression levels of PLAU, SLC2A1, and CA9 exhibited significant associations with prognosis in pancreatic cancer. The prognostic model, built upon these genes, displayed robust predictive accuracy and was validated in an independent dataset. Furthermore, we found a correlation between the risk score of the prognostic model and clinical parameters of pancreatic cancer patients. At the same time, we also explored the relationship between the established hypoxia-related prognostic model and the immune microenvironment at the single-cell level. RT-qPCR results showed notable differences in the expression of hypoxia pathway-related genes between normal PANC-1 and hypoxic-treated PANC-1 cells.
Our study provides insights into the role of the hypoxic microenvironment in pancreatic cancer and offers a promising prognostic tool for clinical application.
胰腺癌具有侵袭性和预后不良的特点,常伴有隐匿的早期症状,给治疗带来了巨大的挑战。肿瘤微环境(TME)在胰腺癌的进展和治疗反应中起着关键作用,其特点是缺氧和免疫抑制。本研究旨在利用这些基因识别与缺氧相关的基因,并为胰腺癌开发一个预后模型。
通过对癌症基因组图谱(TCGA)的基因表达数据进行分析,并进行随后的 GO/KEGG 富集分析,确定了与缺氧相关的途径。我们使用lasso 回归构建了一个预后模型,并使用独立数据集进行验证。
我们的结果表明,PLAU、SLC2A1 和 CA9 的表达水平与胰腺癌的预后显著相关。基于这些基因构建的预后模型显示出强大的预测准确性,并在独立数据集得到验证。此外,我们发现该预后模型的风险评分与胰腺癌患者的临床参数之间存在相关性。同时,我们还在单细胞水平上探讨了建立的缺氧相关预后模型与免疫微环境之间的关系。RT-qPCR 结果表明,正常 PANC-1 和缺氧处理的 PANC-1 细胞中缺氧途径相关基因的表达存在显著差异。
本研究深入探讨了缺氧微环境在胰腺癌中的作用,并为临床应用提供了有前途的预后工具。