Gan Siyuan, Li Changfu, Hou Rui, Tian Geng, Zhao Yuan, Ren Dan, Zhou Wenjing, Zhao Fei, Lv Kebo, Yang Jialiang
School of Mathematical Sciences, Ocean University of China, Qingdao, China.
Department of Digestive Internal Medicine, Daqing Longnan Hospital, The Fifth Affiliated Hospital of Qiqihar Medical College, Daqing 163000, China.
Mol Ther Oncol. 2024 Jul 19;32(3):200849. doi: 10.1016/j.omton.2024.200849. eCollection 2024 Sep 19.
Precancerous lesions typically precede gastric cancer (GC), but the molecular mechanisms underlying the transition from these lesions to GC remain unclear. Therefore, it is urgent to understand this transition from precancerous lesions to GC, which is crucial for the early diagnosis and treatment of GC. In this study, we merged multiple single-cell RNA sequencing datasets to investigate the molecular changes in distinct cell types associated with the progression of GC. First, we observed an increasing abundance of immune cells and a decrease in non-immune cells from non-atrophic gastritis to GC. Five immune cell types were significantly enriched in GC compared to precancerous lesions. Moreover, we found that the interleukin (IL)-17 signaling pathway and Th17 cell differentiation were significantly up-regulated in immune cell subsets during GC progression. Some genes in these processes were predominantly expressed at the GC stage, highlighting their potential as diagnostic markers. Furthermore, we validated our findings using bulk RNA sequencing data from The Cancer Genome Atlas and confirmed consistent immune cell changes during GC progression. Our study provides insights into the immune infiltration and signaling pathways involved in the development of GC, contributing to the development of early diagnosis and targeted treatment strategies for this malignancy.
癌前病变通常先于胃癌（GC）出现，但这些病变向GC转变的分子机制仍不清楚。因此，迫切需要了解这种从癌前病变到GC的转变，这对GC的早期诊断和治疗至关重要。在本研究中，我们合并了多个单细胞RNA测序数据集，以研究与GC进展相关的不同细胞类型的分子变化。首先，我们观察到从非萎缩性胃炎到GC，免疫细胞丰度增加而非免疫细胞减少。与癌前病变相比，五种免疫细胞类型在GC中显著富集。此外，我们发现白细胞介素（IL）-17信号通路和Th17细胞分化在GC进展过程中的免疫细胞亚群中显著上调。这些过程中的一些基因主要在GC阶段表达，突出了它们作为诊断标志物的潜力。此外，我们使用来自癌症基因组图谱的批量RNA测序数据验证了我们的发现，并证实了GC进展过程中免疫细胞的一致变化。我们的研究为GC发生过程中涉及的免疫浸润和信号通路提供了见解，有助于开发针对这种恶性肿瘤的早期诊断和靶向治疗策略。
