Byeon Sooin, du Toit-Thompson Taymin, Gillson Josef, Gill Anthony J, Samra Jaswinder S, Mittal Anubhav, Sahni Sumit
Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
Kolling Institute of Medical Research, University of Sydney, Sydney, New South Wales, Australia.
Cancer Med. 2023 Sep;12(17):18020-18031. doi: 10.1002/cam4.6407. Epub 2023 Aug 3.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies in the world, for which the mortality is almost as high as the disease incidence and is predicted to be the second-highest cause of cancer-related deaths by 2030. These cancerous tumors consist of diversified gene expressions within the different cellular subpopulations that include neoplastic ductal cells, cancer-associated fibroblasts, and immune cells, all of which collectively facilitate cellular heterogeneity in the PDAC tumor microenvironment (TME). Active intratumoral interaction within the cell populations in TME induces the proliferation of cancerous cells, accounting for tumorigenesis and rapid metastasis.
This review will focus on novel findings uncovering PDAC heterogeneity in different cellular subpopulations using single-cell RNA-sequencing (scRNA-seq) and other single-cell analysis technologies. It will further explore the emerging role of single-cell technologies in assessing the role of different subpopulations of neoplastic ductal cells, cancer-associated fibroblasts, and immune cells in PDAC progression.
The application of scRNA-seq in PDAC has started to unveil associations between disease progression and heterogeneity in pancreatic TME and could influence future PDAC treatment. Recent advances in scRNA-seq have uncovered comprehensive analyses of heterogeneous ecosystems present within the TME. These emerging findings underpins further need for a more in-depth understanding of intratumoral heterogeneity in the PDAC microenvironment.
胰腺导管腺癌（PDAC）是世界上最致命的恶性肿瘤之一，其死亡率几乎与发病率一样高，预计到2030年将成为癌症相关死亡的第二大原因。这些癌性肿瘤在不同细胞亚群中具有多样化的基因表达，这些亚群包括肿瘤导管细胞、癌症相关成纤维细胞和免疫细胞，所有这些共同促进了PDAC肿瘤微环境（TME）中的细胞异质性。TME中细胞群体之间活跃的肿瘤内相互作用诱导癌细胞增殖，这是肿瘤发生和快速转移的原因。
本综述将聚焦于利用单细胞RNA测序（scRNA-seq）和其他单细胞分析技术揭示不同细胞亚群中PDAC异质性的新发现。它将进一步探讨单细胞技术在评估肿瘤导管细胞、癌症相关成纤维细胞和免疫细胞的不同亚群在PDAC进展中的作用方面的新作用。
scRNA-seq在PDAC中的应用已开始揭示疾病进展与胰腺TME异质性之间的关联，并可能影响未来的PDAC治疗。scRNA-seq的最新进展揭示了对TME中存在的异质生态系统的全面分析。这些新发现进一步表明需要更深入地了解PDAC微环境中的肿瘤内异质性。
