基于单细胞RNA测序数据对胰腺癌肿瘤微环境中缺氧肿瘤亚群的探究

Exploration of Hypoxia-Related Tumor Subpopulations in the Tumor Microenvironment of Pancreatic Cancer Based on Single-Cell RNA-Sequencing Data

摘要: 胰腺癌作为恶性程度极高的肿瘤之一，多数患者确诊时已处于不可切除或转移性阶段。随着单细胞RNA测序(single-cell RNA-sequencing, scRNA-seq)技术的发展，我们能够以更高分辨率深入探索肿瘤微环境(tumor microenvironment, TME)的内部异质性，从而揭示胰腺癌进展中预后不良的关键机制。先前研究指出，缺氧是实体瘤TME的固有特性，能激活血管生成与转移相关的信号通路，但缺氧TME的异质性仍需进一步阐释。通过基因集富集分析、拟时序分析和细胞间通讯分析等手段，对胰腺癌scRNA-seq数据进行分析，识别出具有不同生物学功能的肿瘤亚群，特别是与缺氧密切相关的亚群。该缺氧肿瘤亚群与不良预后紧密相关，据此构建的风险评分模型可有效预测胰腺癌患者总生存期。本研究加深了对胰腺癌TME的了解，为胰腺癌预后的预测提供了一定参考。

Abstract: Pancreatic cancer is one of the most malignant tumors and most patients have unrespectable or metastatic disease at the time of diagnosis. With the development of single-cell RNA-sequencing (scRNA-seq) technology, we are able to explore the internal heterogeneity of the tumor microenvironment (TME) at a higher resolution, thereby revealing the key mechanisms underlying the poor prognosis of pancreatic cancer progression. Previous studies have shown that hypoxia is an intrinsic property of the TME in solid tumors and activates signaling pathways involved in angiogenesis and metastasis, but the heterogeneity of the hypoxic TME remains to be further elucidated. Pancreatic cancer scRNA-seq data were analyzed by gene set enrichment analysis, mimetic temporal sequencing analysis and intercellular communication analysis to identify a subpopulation of tumor s with distinct biological functions, in particular one closely related to hypoxia. This hypoxic tumor subgroup was closely associated with poor prognosis, and the risk score model constructed accordingly could effectively predict the overall survival of pancreatic cancer patients. This study deepens the understanding of TME in pancreatic cancer and provides some guidance for predicting the prognosis of pancreatic cancer.