基于单细胞RNA测序技术探讨胰腺癌异质性的研究进展-国际临床研究杂志-CSCIED科技核心评价数据库-手机版

基于单细胞RNA测序技术探讨胰腺癌异质性的研究进展

Research progress on exploring the heterogeneity of pancreatic cancer based on single-cell RNA sequencing technology

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DOI	10.12208/j.ijcr.20250365
刊名	国际临床研究杂志 International Journal of Clinical Research
年，卷(期)	2025, 9(8)
作者	周聪雅¹,张帆²,于娇¹,张高飞¹*,
作者单位	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
摘要	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。
Abstract	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.
关键词	单细胞RNA测序；胰腺癌；肿瘤微环境；异质性；免疫治疗
KeyWord	Single-cell RNA sequencing; Pancreatic cancer; Tumor microenvironment; Heterogeneity; Immunotherapy
基金项目
页码	4-9

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[1] Siegel RL, Kratzer TB, Giaquinto AN, et al. Cancer statistics, 2025
[J]. CA Cancer J Clin. 2025, 75(1):10-45.
[2] Rahib L, Smith BD, Aizenberg R, et al. Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States
[J]. Cancer Res, 2014, 74(11): 2913-2921.
[3] Kolbeinsson HM, Chandana S, Wright GP, et al. Pancreatic Cancer: A Review of Current Treatment and Novel Therapies
[J]. J Invest Surg, 2023, 36(1): 2129884.
[4] Ansari D, Tingstedt B, Andersson B, et al. Pancreatic cancer: yesterday, today and tomorrow
[J]. Future Oncol, 2016, 12(16): 1929-1946.
[5] 王延磊,王政华. CT引导下~(125)I粒子植入联合吉西他滨、卡培他滨治疗局部进展期胰腺癌临床疗效观察
[J]. 陕西医学杂志,2020,49(12):1604-1607. Yanlei Wang, Zhenghua Wang. Clinical efficacy of CT-guided 125I particle implantation combined with gemcitabine and capecitabine in treatment of locally advanced pancreatic cancer
[J]. Shaanxi Medical Journal, 2020, 49(12):1604-1607.
[6] Zhang X, Marjani SL, Hu Z, et al. Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects
[J]. Cancer Res, 2016, 76(6): 1305-1312.
[7] Wang R, Lin DY, Jiang Y. SCOPE: A Normalization and Copy-Number Estimation Method for Single-Cell DNA Sequencing
[J]. Cell Syst, 2020, 10(5): 445-452.
[8] Shi P, Nie Y, Yang J, et al. Fundamental and practical approaches for single-cell ATAC-seq analysis
[J]. aBIOTECH, 2022, 3(3): 212-223.
[9] Nedwed AS, Helbich SS, Braband KL, et al. Using combined single-cell gene expression, TCR sequencing and cell surface protein barcoding to characterize and track CD4+ T cell clones from murine tissues
[J]. Front Immunol, 2023, 14: 1241283.
[10] Potter SS. Single-cell RNA sequencing for the study of development, physiology and disease
[J]. Nat Rev Nephrol, 2018, 14(8): 479-492.
[11] Tang F, Barbacioru C, Wang Y, et al. mRNA-Seq whole-transcriptome analysis of a single cell
[J]. Nat Methods, 2009, 6(5): 377-382.
[12] Davis RT, Blake K, Ma D, et al. Transcriptional diversity and bioenergetic shift in human breast cancer metastasis revealed by single-cell RNA sequencing
[J]. Nat Cell Biol, 2020, 22(3): 310-320.
[13] Zhou Y, Yang D, Yang Q, et al. Single-cell RNA landscape of intratumoral heterogeneity and immunosuppressive microenvironment in advanced osteosarcoma
[J]. Nat Commun, 2020, 11(1): 6322.
[14] Wang J, Ren M, Yu J, et al. Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer
[J]. EBioMedicine, 2022, 85:104319.
[15] Schlesinger Y, Yosefov-Levi O, Kolodkin-Gal D, et al. Single-cell transcriptomes of pancreatic preinvasive lesions and cancer reveal acinar metaplastic cells' heterogeneity
[J]. Nat Commun, 2020, 11(1): 4516.
[16] Bernard V, Semaan A, Huang J, et al. Single-Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression
[J]. Clin Cancer Res, 2019, 25(7): 2194-2205.
[17] Peng J, Sun BF, Chen CY, et al. Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma
[J]. Cell Res, 2019, 29(9): 725-738.
[18] Moncada R, Barkley D, Wagner F, et al. Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas
[J]. Nat Biotechnol, 2020, 38(3): 333-342.
[19] Fan X, Lu P, Wang H, et al. Integrated single-cell multiomics analysis reveals novel candidate markers for prognosis in human pancreatic ductal adenocarcinoma
[J]. Cell Discov, 2022, 8(1): 13.
[20] Dimitrov-Markov S, Perales-Patón J, Bockorny B, et al. Discovery of New Targets to Control Metastasis in Pancreatic Cancer by Single-cell Transcriptomics Analysis of Circulating Tumor Cells
[J]. Mol Cancer Ther, 2020, 19(8): 1751-1760.
[21] Makohon-Moore AP, Zhang M, Reiter JG, et al. Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer
[J]. Nat Genet, 2017, 49(3): 358-366.
[22] Carstens JL, Yang S, Correa de Sampaio P, et al. Stabilized epithelial phenotype of cancer cells in primary tumors leads to increased colonization of liver metastasis in pancreatic cancer
[J]. Cell Rep, 2021, 35(2): 108990.
[23] Raghavan S, Winter PS, Navia AW, et al. Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer
[J]. Cell, 2021, 184(25): 6119-6137.
[24] Werba G, Weissinger D, Kawaler EA, et al. Single-cell RNA sequencing reveals the effects of chemotherapy on human pancreatic adenocarcinoma and its tumor microenvironment
[J]. Nat Commun, 2023, 14(1): 797.
[25] Wang L, Liu Y, Dai Y, et al. Single-cell RNA-seq analysis reveals BHLHE40-driven pro-tumour neutrophils with hyperactivated glycolysis in pancreatic tumour microenvironment
[J]. Gut, 2023, 72(5): 958-971.
[26] Zhang S, Fang W, Zhou S, et al. Single cell transcriptomic analyses implicate an immunosuppressive tumor microenvironment in pancreatic cancer liver metastasis
[J]. Nat Commun, 2023, 14(1): 5123.
[27] Chen K, Wang Y, Hou Y, et al. Single cell RNA-seq reveals the CCL5/SDC1 receptor-ligand interaction between T cells and tumor cells in pancreatic cancer
[J]. Cancer Lett, 2022, 545: 215834.
[28] Sang W, Zhou Y, Chen H, et al. Receptor-interacting protein kinase 2 is an immunotherapy target in pancreatic cancer
[J]. Cancer Discov, 2024, 14(2):326-347.
[29] Wang X, Hu LP, Qin WT, et al. Identification of a subset of immunosuppressive P2RX1-negative neutrophils in pancreatic cancer liver metastasis
[J]. Nat Commun, 2021, 12(1): 174.
[30] Lin W, Noel P, Borazanci EH, et al. Single-cell transcriptome analysis of tumor and stromal compartments of pancreatic ductal adenocarcinoma primary tumors and metastatic lesions
[J]. Genome Med, 2020, 12(1): 80.

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周聪雅,张帆,于娇,张高飞*. 基于单细胞RNA测序技术探讨胰腺癌异质性的研究进展 [J]. 国际临床研究杂志. 2025; 9; (8). 4 - 9.

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