神经内分泌前列腺癌裸鼠模型肿瘤进展中相关成纤维细胞基因表达变化的测序分析  

RNA sequencing analysis of gene expression changes of cancer-related fibroblasts during cancer progression in nude mouse model of neuroendocrine prostate cancer

作　　者：谢弘[1] 傅强[1] 胡晓勇[1] 张炯[1] 宋鲁杰[1] 黄建文[1] 杨涛[1] XIE Hong;FU Qiang;HU Xiaoyong;ZHANG Jiong;SONG Lujie;HUANG Jianwen;YANG Tao(Department of Urology,Shanghai Jiaotong University Affiliated Sixth People's Hospital,Shanghai 200233;Shanghai Eastern Urological Reconstruction and Repair Institute,Shanghai 200233,China)

机构地区：[1]上海交通大学附属第六人民医院泌尿外科,上海东方泌尿修复重建研究所,上海200233

出　　处：《现代泌尿外科杂志》2022年第12期1059-1063,1073,共6页Journal of Modern Urology

基　　金：上海市科学技术委员会资助项目(No.19140901702)。

摘　　要：目的分析动物模型中神经内分泌前列腺癌(NEPC)肿瘤种植后不同时期肿瘤相关成纤维细胞基因表达的变化情况及其潜在意义。方法通过建立NEPC移植裸鼠模型,分别于2周、4周处死后取出裸鼠模型瘤灶,分离培养肿瘤相关性成纤维细胞,利用转录组测序技术(RNA-seq)宏观分析差异表达的基因,运用相关生物信号分析相关差异基因及信号通路,应用定量PCR法对部分差异表达基因进行验证。结果NEPC不同时期相关成纤维细胞出现部分基因表达增强或抑制,主要富集于细胞外环境及肿瘤信号通路,此外肿瘤转录失调通路、肿瘤血管新生、脂蛋白代谢等通路亦有变化。通过qPCR验证部分差异性基因,发现以NKX3-1、ISM1基因为代表的相关通路基因在4周组显著低于2周组,而随着肿瘤进展GREM1基因的表达显著增加(P<0.01)。结论NEPC相关成纤维细胞在不同时象中相关基因的表达存在差异性,其中NKX3-1、ISM1、GREM1基因等可能在肿瘤相关性成纤维细胞促进肿瘤进展病理过程中发挥潜在作用。Objective To explore the changes of gene expression of cancer-related fibroblasts in different stages after implantation of neuroendocrine prostate cancer in animal model.Methods After the models of neuroendocrine prostate cancer were established,the mice were killed at week 2 and 4,respectively.The cancer foci were removed,and cancer-related fibroblasts were isolated and cultured.The differentially expressed genes were analyzed with transcriptome sequencing(RNA seq),and related biological signal pathways were re-analyzed with software.Then some differentially expressed genes were verified with quantitative PCR(qPCR).Results In different stages of neuroendocrine prostate cancer,the expression of some genes in related fibroblasts was enhanced or inhibited,which was mainly concentrated in the extracellular environment and tumor signal pathway.In addition,it was also related to cancer transcriptional imbalance pathway,cancer angiogenesis and lipoprotein metabolism pathway.Results of qPCR showed that the related pathway genes represented by NKX3-1 and ISM1 gene in the 4-week group were significantly lower than those in the 2-week group,and the expression of GREM1 gene increased significantly with cancer progression(P<0.01).Conclusion The expression of genes in neuroendocrine prostate cancer-related fibroblasts is differentially expressed in different time images.NKX3-1,ISM1 and GREM1 genes may be involved in regulating cancer-related fibroblasts and promoting the pathological process of cancer progression.

关 键 词：前列腺肿瘤 神经内分泌 癌相关成纤维细胞 RNA测序 裸鼠 

分 类 号：R137[医药卫生—劳动卫生]