Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq

PAN Yuwei; TAN Yuting; XUE Rui; CHU Zhaole; LIU Biying; LI Xianfeng; WANG Tao; WANG Bin; ZHANG Xuan; YANG Yongtao

doi:10.16016/j.2097-0927.202411050

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Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq

Monographic Reports | 更新时间：2025-03-11

- Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq
- Journal of Army Medical University Vol. 47, Issue 5, Pages: 443-452(2025)
- 作者机构：
  
  1.重庆大学医学院，重庆
  2.重庆大学附属肿瘤医院消化内科，重庆
  3.陆军特色医学中心（第三军医大学大坪医院）消化内科，消化系统肿瘤精准防治重庆市重点实验室，重庆
  4.重庆市中医院肿瘤科，重庆
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Excellent Young Scientists of China(81822032);the Natural Science Foundation for Distinguished Young Scholars of Chongqing(CSTC2019JCYJJQX0027)
- DOI：10.16016/j.2097-0927.202411050
  CLC： R394.3;R730.7;R735.2
- Received：12 November 2024，
  
  Revised：06 January 2025，
  
  Published：15 March 2025
- 稿件说明：
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潘雨薇，谭玉婷，薛锐，等.基于普通转录组和单细胞转录组测序解析间质型胃癌复发风险相关的肿瘤细胞及微环境特征［J］.陆军军医大学学报，2025，47（05）：443-452.DOI：10.16016/j.2097-0927.202411050.

PAN Y W，TAN Y T，XUE R，et al.Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq［J］.J Army Med Univ，2025，47（05）：443-452.DOI：10.16016/j.2097-0927.202411050.
潘雨薇，谭玉婷，薛锐，等.基于普通转录组和单细胞转录组测序解析间质型胃癌复发风险相关的肿瘤细胞及微环境特征［J］.陆军军医大学学报，2025，47（05）：443-452.DOI：10.16016/j.2097-0927.202411050. DOI：

PAN Y W，TAN Y T，XUE R，et al.Features of tumor cells and microenvironment associated with recurrence risk of mesenchymal-subtype gastric cancer based on bulk RNA-seq and scRNA-seq［J］.J Army Med Univ，2025，47（05）：443-452.DOI：10.16016/j.2097-0927.202411050. DOI：

摘要

目的

整合多组学数据解析间质型胃癌（mesenchymal-subtype gastric cancer，Mes-GC）临床特性，探究与间质型胃癌复发风险相关的肿瘤细胞及微环境特征。

方法

收集2022年1月至2023年12月，在陆军特色医学中心消化内科就诊患者的组织样本，包括19例弥漫型胃癌、22例肠型胃癌与23例混合型胃癌患者的组织，用于转录组和基因组测序；整合包括癌症基因组图谱（The Cancer Genome Atlas，TCGA）、美国国立生物技术信息中心基因表达数据库（Gene Expression Omnibu，GEO）以及国家基因组科学中心（National Genomics Data Center，NGDC）数据库资源，采用生物信息学分析，比较间质型胃癌与非间质型胃癌在临床特性以及肿瘤微环境特征等方面的异同。

结果

相比非间质型胃癌，间质型胃癌临床分期较晚、肿瘤浸润程度深、淋巴结转移率高（

0.05）；Kaplan-Meier生存分析表明间质型胃癌生存期短、极易复发、临床预后差（

0.05）；单细胞转录组测序（single-cell RNA sequencing，scRNA-seq）数据分析揭示了间质型胃癌肿瘤细胞高表达干性、转移以及上皮-间质转化（epithelial-mesenchymal transition，EMT）相关基因，肿瘤微环境中髓系细

胞、平滑肌细胞、内皮细胞和成纤维细胞显著升高，其中成纤维细胞含量升高最为明显（

0.05），且成纤维细胞含量越高患者预后越差。

结论

间质型胃癌肿瘤细胞具有较高的干性和EMT特征，肿瘤微环境中富集髓系细胞、内皮细胞和成纤维细胞等间质细胞，这些特征可能是导致间质型胃癌预后差、易复发的关键因素。

Abstract

Objective‍　‍To analyze clinical characteristics of mesenchymal-subtype gastric cancer (Mes-GC) by integrating multi-omics data and explore the characteristics of tumor cells and microenvironment associated with the risk for recurrence. Methods‍　‍Gastric tumor tissue samples were collected from the patients who visited Department of Gastroenterology of Army Medical Center of PLA from January 2022 to December 2023. Transcriptome and genome sequencing were applied for these tissue samples

including 19 cases of diffuse-type gastric cancer

22 cases of intestinal-type gastric cancer

and 23 cases of mixed-type gastric cancer patients. Bioinformatics analysis was employed to investigate the differences in clinical characteristics and tumor microenvironment between Mes-GC and non-mesenchymal-subtype gastric cancer (non-Mes-GC) by integrating data resources including The Cancer Genome Atlas (TCGA)

Gene Expression Omnibus (GEO)

and National Genomics Data Center (NGDC). Results‍　‍Compared to non-Mes-GC patients

Mes-GC ones were characterized by later clinical stages

deeper tumor infiltration

and higher rates of lymph node metastasis. Kaplan-Meier survival analysis confirmed that Mes-GC patients were associated with shorter survival time

poor prognosis as well as increased risk of cancer recurrence （

0.05）. Single-cell RNA sequencing data revealed that tumor cells in Mes-GC showed higher expression levels of the genes related to stemness

metastasis （

0.05）

and epithelial-mesenchymal transition (EMT). And in the tumor microenvironment

there were significant more myeloid cells

smooth muscle cells

endothelial cells and fibroblasts

with the most pronounced elevation in the proportion of fibroblasts （

0.05）. Moreover

the patients with larger proportion of fibroblasts were associated with poorer prognosis. Conclusion‍　‍Mes-GC tumor cells exhibit higher stemness and EMT characteristics

and stromal cells such as myeloid cells

endothelial cells

and fibroblasts are enriched in the tumor microenvironment. These features may be key factors contributing to poor prognosis and high recurrence rate of Mes-GC.

关键词

Keywords

references

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