浙江医学2025，Vol.47Issue(22)：2394-2398,2408,后插2-后插4,9.DOI:10.12056/j.issn.1006-2785.2025.47.22.2025-1330
基于多组学分析FBXO3在肾透明细胞癌中的表达及其临床和免疫特征
Multi-omics analysis on FBXO3 in kidney renal clear cell carcinoma:expression profile and its clinical and immunological char-acteristics
摘要
Abstract
Objective To perform a multi-omics analysis on F-box protein(FBXO)3 expression in kidney renal clear cell carcinoma(KIRC)and to explore its clinical and immunological characteristics.Methods FBXO3 expression differences in KIRC were analyzed using The Cancer Genome Atlas,Gene Expression Omnibus,and Clinical Proteomic Tumor Analysis Consortium databases,and its correlation with clinical characteristics was evaluated in combination with clinicopathological features.Kaplan-Meier survival analysis and Cox proportional hazards regression models were applied to analyze its impact on patient survival.Gene set enrichment analysis was used to identify potential biological functions of FBXO3.The relationship between FBXO3 and immune cell infiltration was evaluated by using algorithms for estimating tumor tissue stroma and immune cell components,analyzing tumor immune cell infiltration resources,and calculating the relative proportion of immune cell subsets.Immunopheno Score(IPS)and tumor mutation burden(TMB)analyses were conducted to investigate the association of FBXO3 with immunotherapy responsiveness.Tumor and adjacent normal tissues were collected from 20 KIRC patients who underwent radical nephrectomy at Zhuzhou Hospital Affiliated to Xiangya School of Medicine,Central South University between January 2024 and January 2025,and their immune scores were compared by immunohistochemistry.Results The transcript levels,mRNA and protein expression,and promoter methylation of FBXO3 in KIRC tissues were significantly lower than those in normal renal tissues,and were significantly associated with clinicopathological factors such as sex,histological grade,clinical stage,T stage,and M stage(all P＜0.01).Patients with low FBXO3 expression had significantly lower overall survival(OS),progression-free survival,and disease-specific survival compared with the high-expression group(all P＜0.01),and low FBXO3 expression was identified as an independent risk factor for OS in KIRC(HR=0.643,P=0.006).Low FBXO3 expression was mainly enriched in pathways including endocytosis,olfactory transduction,spliceosome,ubiquitin-mediated proteolysis,and valine,leucine,and isoleucine degradation.FBXO3 expression was positively correlated with several key immune checkpoint genes,including PDCD1LG2,CD274,CD28,CD48,and hepatitis A virus cellular receptor 2,but negatively correlated with lymphocyte activation gene 3.FBXO3 expression showed no significant correlation with TMB(rs=-0.062,P＞0.05).Under various immunotherapy combination states[cytotoxic T-lymphocyte-associated antigen 4(CTLA4)+programmed cell death protein 1(PD1)+,CTLA4-PD1+,CTLA4+PD1+],the high FBXO3 expression group had significantly higher IPS than the low-expression group(all P＜0.05).Immunohistochemical validation showed that the immune score of KIRC tissues was significantly lower than that of adjacent normal tissues(P＜0.001).Conclusion FBXO3 is downregulated in KIRC and may serve as a potential prognostic biomarker and immunotherapeutic target,providing important implications for the diagnosis and individualized treatment of KIRC.关键词
F-box蛋白3/肾透明细胞癌/预后/免疫微环境/免疫治疗/生物信息学Key words
FBXO3/Kidney renal clear cell carcinoma/Prognosis/Immune microenvironment/Immunotherapy/Bioinformatics引用本文复制引用
王芸,易梓瑞,瞿根义,柳成孟..基于多组学分析FBXO3在肾透明细胞癌中的表达及其临床和免疫特征[J].浙江医学,2025,47(22):2394-2398,2408,后插2-后插4,9.基金项目
湖南省自然科学基金项目(2024JJ7660) （2024JJ7660）
