International Journal of Clinical Research
International Journal of Clinical Research. 2025; 9: (8) ; 10.12208/j.ijcr.20250365 .
总浏览量: 53
1 陕西省人民医院放疗科 陕西西安
2 陕西省人民医院肿瘤内科 陕西西安
*通讯作者： 张高飞,单位： 陕西省人民医院放疗科 陕西西安；
胰腺癌是致死率极高的恶性肿瘤，目前临床上针对胰腺癌的主要治疗手段为手术、放疗和化疗，由于其肿瘤异质性及肿瘤微环境（Tumor microenvironment, TME）异质性的存在，使得免疫治疗效果十分有限。传统的高通量测序存在无法揭示肿瘤异质性的局限性，而单细胞RNA测序（single-cell RNA sequencing，scRNA-seq）在单个细胞水平揭示同一肿瘤内不同细胞之间的变异程度与相互联系，达到从基因层面研究细胞之间变异程度的目的。其在探索肿瘤异质性、发现新的细胞亚群以及分析TME中细胞间相互作用关系方面具有很大优势。本研究就scRNA-seq在绘制胰腺癌图谱、挖掘胰腺癌肿瘤和TME异质性、鉴定关键细胞亚群以及提供新的治疗靶点等方面进行深入分析，scRNA-seq鉴定2型导管细胞是胰腺癌的恶性细胞群，鉴定了7个肿瘤相关中性粒细胞（Tumor associated neutrophils, TANs）亚群，其中TAN-1为促肿瘤亚群，提出了靶向CCL5/SDC1轴可能对胰腺癌治疗有效；靶向RIPK2联合免疫治疗可能成为胰腺癌新型治疗策略，本研究旨在为胰腺癌scRNA-seq尝试开发研究提供理论参考。
Pancreatic cancer, a highly fatal malignant tumor, is currently treated through surgery, radiotherapy, and chemotherapy. The effectiveness of immunotherapy is limited due to the heterogeneity of the tumor and tumor microenvironment (TME). Traditional high-throughput sequencing fails to reveal tumor heterogeneity, while single-cell RNA sequencing (scRNA-seq) enables the study of genetic variation and interconnection between cells in the tumor. This technology has significant advantages in exploring tumor heterogeneity, identifying new cell subpopulations, and analyzing cell-cell interactions in the TME. This study provides an in-depth analysis of the role of scRNA-seq technology in mapping pancreatic cancer, exploring intratumoral and microenvironmental heterogeneity of tumor and TME, identifying key cell subclusters and providing new therapeutic targets. The study identified type 2 ductal cells as the malignant cell population in pancreatic cancer tissues and 7 tumor-associated neutrophil (TANs) subpopulations, among which TAN-1 is a tumor-promoting subpopulation. It was proposed that targeting the CCL5/SDC1 axis may be effective in the treatment of pancreatic cancer. Targeted RIPK2 combined with immunotherapy may become a new therapeutic strategy for pancreatic cancer. The findings aim to serve as a theoretical reference for further research on single-cell sequencing technology in pancreatic cancer.
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