nav emailalert searchbtn searchbox tablepage yinyongbenwen piczone journalimg journalInfo journalinfonormal searchdiv searchzone qikanlogo popupnotification paper paperNew
2026, 02, v.29 85-90
基于转录组测序的胃癌关键基因识别与影响机制分析
基金项目(Foundation): 国家自然科学基金资助项目(82073271)
邮箱(Email): 408960337@qq.com;
DOI:
摘要:

目的:基于转录组测序(RNA-Seq)技术筛选胃癌(GC)进展关键基因,并推测其影响GC进展的潜在机制。方法:收集晚期GC腹膜转移患者行腹腔热灌注化疗(HIPEC)治疗前后大网膜转移结节进行高通量RNA测序,对差异表达基因进行GO和KEGG富集分析;qRT-PCR检测上调倍数最大的前10个基因在治疗前后的mRNA变化;通过siRNA技术抑制HGC27细胞系中关键基因A1CF的表达,采用MTT实验、细胞克隆形成实验及Transwell实验检测A1CF对GC细胞增殖和侵袭能力的影响。结果:HIPEC后,共有2087个基因上调,875个基因下调。差异基因主要功能富集在MAPK通路、NOD样受体通路和TNF通路等。在上调倍数最大的10个基因中,治疗后FOSB、DEFA5、EGR3、A1CF的mRNA水平显著上升。细胞实验显示,抑制关键基因A1CF后GC细胞的增殖和侵袭能力明显减弱(P<0.05)。结论:FOSB、DEFA5、EGR3、A1CF是GC进展的关键基因,A1CF能够驱动GC细胞增殖与侵袭过程,促进GC进展。

Abstract:

Objective: To delineate the differential gene expression profiles in patients with advanced gastric cancer(GC) and peritoneal metastasis before and after hyperthermic intraperitoneal chemotherapy(HIPEC) using RNA sequencing(RNA-Seq), thereby identifying pivotal genes implicated in GC progression and elucidating the mechanistic role of A1 CFin promoting GC cell proliferation and invasion, so as to provide new potential targeted therapy strategies for advanced GC patients. Methods: Omentum metastatic nodules were collected from advanced GC patients with peritoneal metastasis pre-and post-HIPEC for RNA-Seq analysis. Differentially expressed genes(DEGs) were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses. The top 10 most upregulated genes were validated via qRT-PCR to assess mRNA expression changes. A1 CF expression was silenced in HGC27 cells using siRNA, followed by functional assays including MTT, colony formation, and transwell experiments to evaluate its impact on GC cell proliferation and invasion. Results: HIPEC treatment induced significant alterations in gene expression, with 2,087 genes upregulated and 875 genes downregulated. DEGs were predominantly enriched in pathways including MAPK signaling, NOD-like receptor signaling, and TNF signaling. Among the top 10 upregulated genes, FOSB, DEFA5, EGR3, and A1 CF exhibited markedly elevated mRNA levels post-treatment. Functional inhibition of A1 CF substantially attenuated the proliferative and invasive capacities of GC cells(P<0.05). Conclusion: FOSB, DEFA5, EGR3, and A1 CF are key genes in the progression of gastric cancer(GC), and A1 CF can drive the proliferation and invasion of GC cells to promote the progression of GC.

参考文献

[1]Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022:GLOBOCAN estimates of incidence and mortality worldwide for 36cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3):229-263.DOI:10.3322/caac.21834.

[2]Thrift A P, El-Serag H B. Burden of Gastric Cancer[J]. Clin Gastroenterol Hepatol, 2020, 18(3):534-542. DOI:10.1016/j. cgh. 2019.07.045.

[3]Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022[J]. J Natl Cancer Ctr, 2024, 4(1):47-53. DOI:10.1016/j.jncc.2024.01.006.

[4]朱文帅,孙菁果,鲁艺,等.GLI1表达与肿瘤免疫浸润及胃癌临床预后的关系[J].中国现代普通外科进展,2024,27(1):8-13. DOI:10.3969/j.issn.1009-9905.2024.01.002.

[5]Guan W L, He Y, Xu R H. Gastric cancer treatment:recent progress and future perspectives[J]. J Hematol Oncol, 2023, 16(1):57. DOI:10.1186/s13045-023-01451-3.

[6]詹宏杰,梁寒.腹腔热灌注化疗在腹膜癌中的应用现状[J].肿瘤防治研究,2021,48(4):327-332. DOI:10.3971/j. issn. 1000-8578.2021.20.1280.

[7]张国胜,等.围手术期腹腔热灌注对进展期胃癌的疗效分析[J].中国现代普通外科进展,2013,16(11):896-898. DOI:10.3969/j.issn.1009-9905.2013.11.018.

[8]李雁,周云峰,谢丛华,等.细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移癌的临床研究[J].中国肿瘤临床,2012,39(22):1734-1740. DOI:10.3969/j.issn.1000-8179.2012.22.012.

[9]梁寒.腹腔热灌注化疗技术临床应用专家共识(2016版)解读——胃癌腹膜转移的防治[J].临床外科杂志,2017,25(1):20-23. DOI:10.3969/j.issn.1005-6483.2017.01.004.

[10]陆俊,吕陈彬,曹毅,等.胃癌术后早期复发影响因素及预后分析的全国多中心研究[J].中华消化外科杂志,2025,24(3):350-356. DOI:10.3760/cma.j.cn115610-20241226-00583.

[11]Liu Y, Ding W, Wang J, et al. Non-coding RNA-mediated modulation of ferroptosis in cardiovascular diseases[J]. Biomed Pharmacother, 2023, 164:114993. DOI:10.1016/j.biopha.2023.114993.

[12]Gysin S, Salt M, Young A, et al. Therapeutic strategies for targeting ras proteins[J]. Genes Cancer, 2011, 2(3):3593-3572. DOI:10.1177/1947601911412376.

[13]Karnoub A E, Weinberg R A. Ras oncogenes:split personalities[J].Nat Rev Mol Cell Biol, 2008, 9(7):5175-5231. DOI:10.1038/nrm2438.

[14]Wu Z, Ding Z, Cheng B, et al. The inhibitory effect of human DEFA5 in growth of gastric cancer by targeting BMI1[J]. Cancer Sci, 2021, 112(3):1075-1083.DOI:10.1111/cas.14827.

[15]Liao F, Ji M Y, Shen L, et al. Decreased EGR3 expression is related to poor prognosis in patients with gastric cancer[J]. J Mol Histol,2013, 44(4):463-468.DOI:10.1007/s10735-013-9493-8.

[16]Tang C, Jiang Y, Shao W, et al. Abnormal expression of FOSB correlates with tumor progression and poor survival in patients with gastric cancer[J]. Int J Oncol, 2016, 49(4):1489-1496. DOI:10.3892/ijo.2016.3661.

[17]Ni D, Liu J, Hu Y, et al. A1CF-Axin2 signal axis regulates apoptosis and migration in Wilms tumor-derived cells through Wnt/β-catenin pathway[J]. In Vitro Cell Dev Biol Anim, 2019, 55(4):252-259. DOI:10.1007/s11626-019-00335-6.

[18]Huang L, Wang H, Zhou Y, et al. Apobec-1 Complementation Factor(A1CF)Inhibits Epithelial-Mesenchymal Transition and Migration of Normal Rat Kidney Proximal Tubular Epithelial Cells[J]. Int J Mol Sci, 2016, 17(2):197. DOI:10.3390/ijms17020197.

[19]王程,冯爱露,陈韦璁,等.真核表达质粒pcDNA3.1(+)-A1CF的构建及在肺癌中的表达[J].徐州医科大学学报,2022,42(1):51-56. DOI:10.3969/j.issn.2096-3882.2022.01.011.

[20]甄茂川,刘平果,苏永杰,等.肝细胞肝癌组织中A1CF、UPF1的表达及临床意义[J].国际检验医学杂志,2023,44(19):2423-428.DOI:10.3969/j.issn.1673-4130.2023.19.024.

[21]Li Z, Liu C, Wang M, et al. Cholesterol confers resistance to Apatinib-mediated ferroptosis in gastric cancer[J]. Cell Biosci,2025, 15(1):95. DOI:10.1186/s13578-025-01435-5.

[22]Peng J, Yin Y, Liu X, et al. CD51 promotes gastric cancer stemness via blocking Numb-mediated Notch1 degradation[J]. Cancer Lett,2025, 629:217886. DOI:10.1016/j.canlet.2025.217886.

基本信息:

中图分类号:R735.2

引用信息:

[1]阔文蕾,高根旺,赵伟,等.基于转录组测序的胃癌关键基因识别与影响机制分析[J].中国现代普通外科进展,2026,29(02):85-90.

基金信息:

国家自然科学基金资助项目(82073271)

发布时间:

2026-02-15

出版时间:

2026-02-15

检 索 高级检索

引用

GB/T 7714-2015 格式引文
MLA格式引文
APA格式引文