Significance of dysregulated M2 macrophage and ESR2 in the ovarian metastasis of gastric cancer

被引:1
|
作者
Gao, Jianpeng [1 ,2 ]
Zhao, Zhenxiong [1 ,2 ]
Pan, Hongda [1 ,2 ]
Huang, Yakai [1 ,2 ]
机构
[1] Fudan Univ, Shanghai Canc Ctr, Dept Gastr Surg, 270 Dongan Rd, Shanghai 200032, Peoples R China
[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Gastric cancer (GC); ovarian metastasis (OM); M2; macrophage; estrogen receptor (3 (ER (3 ); ESTROGEN-RECEPTOR-BETA; PLUS CHEMOTHERAPY CHEMO; KRUKENBERG TUMORS; EXPRESSION; MANAGEMENT; DIAGNOSIS; SURVIVAL; ALPHA;
D O I
10.21037/tcr-24-124
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Prognosis of gastric cancer (GC) patients with ovarian metastasis (OM) remains poor. We hereby characterized the role of tumor immune microenvironment (TIME) and identified potential key regulators in the OM with the aim of understanding its molecular basis to develop novel therapeutic targets. Methods: Transcriptomic analyses of paired primary and ovarian metastatic lesions of seven GC patients from Fudan University Shanghai Cancer Center uncovered and functionally annotated their differentially expressed genes (DEGs). CIBERSORT analysis revealed differential TIME between primary GCs and OMs, which was further validated by multiplex immunofluorescence (mIF). Unique overexpression of candidate regulator in OMs was validated by an immunohistochemical (IHC) staining-based cohort study and in vitro cell growth, migration and invasion assays were conducted to characterize its function in GC progression. Results: Functional enrichment analyses of DEGs between GCs and matched OMs revealed multiple significantly dysregulated immune-related and cancer-related pathways. Distinctive subsets of immune cells, especially M2 macrophage, were selectively enriched in metastatic lesions. mIF-based quantification further validated the overexpression of CD68+CD206+ M2 macrophage in the OMs. Estrogen receptor 2 (ESR2), which encodes estrogen receptor (3 (ER(3), was not only potentially correlated with M2 macrophage but also overexpressed in the OM of GC. ESR2 was up-regulated in cancerous tissue and its high expression correlated with younger age, more advanced lymph node metastasis and pathological stage, as well as a worse patient survival. IHC staining of ER(3 in the cohort of paired primary and metastatic GCs validated its selective overexpression in OMs. Small-interfering RNAs (siRNAs)-induced knockdown of ESR2 significantly inhibited the invasion and migration of both AGS and HGC-27 GC cell lines. Conclusions: Comparative RNA-sequencing analysis revealed the dysregulated TIME, M2 macrophage in particular, between primary GC and OM. ESR2 potentially correlated with M2 macrophage and played prooncogenic roles in GC progression and metastasis.
引用
收藏
页码:2674 / 2690
页数:18
相关论文
共 50 条
  • [11] Clinical significance of CD204-positive M2 macrophage in colorectal cancer
    Fushimi, S.
    Matsumoto, M.
    Takahashi, S.
    Ogino, T.
    Itakura, J.
    Ito, T.
    Matsukawa, A.
    VIRCHOWS ARCHIV, 2012, 461 : S177 - S178
  • [12] Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein
    Yulei Chen
    Siyuan Zhang
    Qizhi Wang
    Xiaobo Zhang
    Journal of Hematology & Oncology, 10
  • [13] Tumor-recruited M2 macrophages promote gastric and breast cancer metastasis via M2 macrophage-secreted CHI3L1 protein
    Chen, Yulei
    Zhang, Siyuan
    Wang, Qizhi
    Zhang, Xiaobo
    JOURNAL OF HEMATOLOGY & ONCOLOGY, 2017, 10 : 1 - 13
  • [14] Identification of Potential Prognostic Biomarkers Associated With Macrophage M2 Infiltration in Gastric Cancer
    Liu, Baohong
    Ma, Xueting
    Ha, Wei
    FRONTIERS IN GENETICS, 2022, 13
  • [15] Ganodermanontriol regulates tumor-associated M2 macrophage polarization in gastric cancer
    Zhang, Likang
    Shi, Pinghui
    Jin, Peng
    Chen, Zhenwei
    Hu, Biwen
    Cao, Chenxi
    Wang, Xiaoguang
    Sheng, Jian
    AGING-US, 2024, 16 (02): : 1390 - 1398
  • [16] Genetic association between HER2 and ESR2 polymorphisms and ovarian cancer: a meta-analysis
    Tang, Liang
    Li, Jianming
    Bao, Meihua
    Xiang, Ju
    Chen, Yiwei
    Wang, Yan
    ONCOTARGETS AND THERAPY, 2018, 11 : 1055 - 1066
  • [17] Integrated analysis of the M2 macrophage-related signature associated with prognosis in ovarian cancer
    Peng, Caijiao
    Li, Licheng
    Luo, Guangxia
    Tan, Shanmei
    Xia, Ruming
    Zeng, Lanjuan
    FRONTIERS IN ONCOLOGY, 2022, 12
  • [18] Collagen type V alpha 2 promotes the development of gastric cancer via M2 macrophage polarization
    Guo, Xin
    Bu, Xiaoqian
    Yuan, Li
    Ji, Lina
    CHINESE JOURNAL OF PHYSIOLOGY, 2023, 66 (02): : 93 - 102
  • [19] M2 Macrophage-Based Prognostic Nomogram for Gastric Cancer After Surgical Resection
    Hu, Jianwen
    Ma, Yongchen
    Ma, Ju
    Yang, Yanpeng
    Ning, Yingze
    Zhu, Jing
    Wang, Pengyuan
    Chen, Guowei
    Liu, Yucun
    FRONTIERS IN ONCOLOGY, 2021, 11
  • [20] Diosmetin inhibits the growth and invasion of gastric cancer by interfering with M2 phenotype macrophage polarization
    Zhang, Faqiang
    Luo, Huan
    JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, 2023, 37 (10)