基础医学论著

FRMD4B在泛癌中的作用及其与预后和免疫微环境的关联*

  • 王子真 ,
  • 许浩 ,
  • 钱格格 ,
  • 李嘉慧 ,
  • 张瑶 ,
  • 柏子健 ,
  • 章雯 ,
  • 李歆怡 ,
  • 芮雨童 ,
  • 陈冰
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  • 皖南医学院病理教研室,安徽芜湖 241002
陈冰

收稿日期: 2025-02-23

  网络出版日期: 2026-04-02

基金资助

*国家级大学生创新创业训练计划项目(202410368008);皖南医学院校级科学研究项目(WK2024XS02)

Role of FRMD4B in pan-cancer and its association with prognosis and immune microenvironment

  • WANG Zizhen ,
  • XU Hao ,
  • QIAN Gege ,
  • LI Jiahui ,
  • ZHANG Yao ,
  • BAI Zijian ,
  • ZHANG Wen ,
  • LI Xinyi ,
  • RUI Yutong ,
  • CHEN Bing
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  • Department of Pathology, Wannan Medical College, Wuhu 241002, China

Received date: 2025-02-23

  Online published: 2026-04-02

摘要

目的: 探究FRMD4B基因在多种癌症中的作用及其与预后、免疫微环境的关系。方法: 从TCGA和UCSC Xena数据库获取33种肿瘤数据,运用Perl和R语言对FRMD4B进行差异分析;评估其与预后、临床表型、肿瘤突变负荷(tumor mutation burden, TMB)、微卫星不稳定性(microsatellite instability, MSI)、免疫浸润等的相关性;通过在线工具探究其突变特征、亚细胞定位等。结果: FRMD4B的mRNA在多种肿瘤组织中表达水平低于相应正常组织(P<0.001);四种生存分析结果显示FRMD4B表达与生存率存在肿瘤特异性关联(P<0.05);临床特征分析表明FRMD4B与肿瘤分期、年龄和性别相关(P<0.05);在部分肿瘤中,FRMD4B与TMB、MSI、基质评分、免疫评分呈现不同相关性(P<0.05);免疫组学分析表明FRMD4B在多种肿瘤中与免疫细胞相关(P<0.001),且与多数免疫相关基因呈正相关;基因富集分析显示FRMD4B基因显著富集于免疫通路及细胞周期相关过程;与其相互作用蛋白包括CYTH1、GPA33、HSPB7、PLEKHA5等;主要定位于细胞质及细胞骨架区域。结论: FRMD4B在多种癌症中起关键作用,与肿瘤发展、患者预后及免疫环境紧密相关。它有望成为癌症精准治疗的潜在生物标志物及治疗靶点。

本文引用格式

王子真 , 许浩 , 钱格格 , 李嘉慧 , 张瑶 , 柏子健 , 章雯 , 李歆怡 , 芮雨童 , 陈冰 . FRMD4B在泛癌中的作用及其与预后和免疫微环境的关联*[J]. 包头医学院学报, 2026 , 42(1) : 47 -55 . DOI: 10.16833/j.cnki.jbmc.2026.01.009

Abstract

Objective: To investigate the role of the FRMD4B gene in various cancers and its association with prognosis, immune microenvironment. Methods: Data of 33 tumors were obtained from TCGA and UCSC Xena databases and analyzed FRMD4B in Perl and R. Evaluated its correlation with prognosis, clinical phenotype, tumor mutation burden (TMB), microsatellite instability (MSI), immune infiltration. And explored its mutational characterization, subcellular localization, and more with online tools. Results: The expression level of FRMD4B mRNA in various tumor tissues was lower than that in corresponding normal tissues (P<0.001). The results of four survival analysis showed that FRMD4B expression was associated with tumor-specific survival (P<0.05). In some tumors, FRMD4 B showed different correlations with TMB, MSI, matrix score and immune score (P<0.05). FRMD4B expression exhibited varying degrees of correlation with TMB, MSI, stromal score and immune score in different tumor types(P<0.05). Immunohistological analysis showed that FRMD4B was significantly correlated with immune cells in a variety of tumors(P<0.001) and positively correlated with the majority of immune-related genes. Gene-set enrichment analysis showed that high expression FRMD4B was significantly enriched in biological processes such as immune pathways and cell cycle. Its mutations were mainly missense mutations. Its interacting proteins included CYTH1, GPA33, HSPB7 and PLEKHA5. The subcellular localization was primarily observed in the cytoplasmic and cytoskeletal regions. Conclusion: FRMD4B plays a critical role in a variety of cancers and is closely related to tumor development, prognosis and immune environment. It may become a potential biomarker and therapeutic target for precision cancer therapy.

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 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024, 74(3): 229-263
[2] Dong F. Pan-cancer molecular biomarkers: a paradigm shift in diagnostic pathology[J].Surg Pathol Clin, 2021, 14(3): 507-516.
[3] 何东宁, 周浩东, 刘畅, 等. MAL2在乳腺癌中的差异表达及预后分析[J]. 暨南大学学报(自然科学与医学版), 2021, 42(2): 128-137.
[4] Matkovich SJ, Van Booven DJ, Cappola TP, et al. Association of an intronic, but not any exonic, FRMD4B sequence variant and heart failure[J]. Clin Transl Sci, 2010, 3(4): 134-139.
[5] Kong Y, Zhao L, Charette JR, et al. An FRMD4B variant suppresses dysplastic photoreceptor lesions in models of enhanced S-cone syndrome and of Nrl deficiency[J]. Hum Mol Genet, 2018, 27(19): 3340-3352.
[6] Klarlund JK, Holik J, Chawla A, et al. Signaling complexes of the FERM domain-containing protein GRSP1 bound to ARF exchange factor GRP1[J]. Journal of Biological Chemistry, 2001, 276(43): 40065-40070.
[7] Sun HL, Ma QY, Bian HG, et al. Novel insight on GRP/GRPR axis in diseases[J]. Biomed Pharmacother, 2023, 161: 114497.
[8] Chen E, Zheng F, Yuan X, et al.The effect of TMEFF2 methylation on the tumor stage and survival outcome of clear cell renal cell carcinoma[J]. Cancer Biomarkers, 2017, 19(2): 207-212.
[9] Zhang X, Meng X, Chen Y, et al. The biology of aging and cancer: frailty, inflammation, and immunity[J]. Cancer Journal, 2017, 23(4): 201-205.
[10] Chan TA, Yarchoan M, Jaffee E, et al. Development of tumor mutation burden as an immunotherapy biomarker:utility for the oncology clinic[J]. Oxford University Press, 2019, 30(1): 44-56.
[11] Styk J, Ps Z, Ps O, et al. Microsatellite instability assessment is instrumental for predictive, preventive and personalised medicine:status quo and outlook[J]. EPMA Journal, 2023, 14(1): 143-165.
[12] Jian X, Sofer T, Tarraf W, et al. Genome-wide association study of cognitive function in diverse Hispanics/latinos:results from the hispanic community health study/study of latinos[J]. Translational Psychiatry, 2020, 10(1): 245.
[13] Chen X, Wang Y, Li Y, et al. Identification of immune-related cells and genes in the breast invasive carcinoma microenvironment[J]. Aging, 2022, 14(3): 1374-1388.
[14] Matimba A, Li F, Livshits A, et al. Thiopurine pharmacogenomics:association of SNPs with clinical response and functional validation of candidate genes[J]. Pharmacogenomics, 2014, 15(4):433-447.
[15] Wen Y, Liming H, Binbin W, et al. Integration of transcriptome and machine learning to identify the potential key genes and regulatory networks affecting drip loss in pork[J]. Journal of Animal Science, 2024, 102: skae164.
[16] Han JS, Hino K, Li W, et al. CRL5-dependent regulation of the small GTPases ARL4C and ARF6 controls hippocampal morphogenesis[J]. Proceedings of the National Academy of Sciences, 2020, 117(37): 23073-23084.
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