RNA结合蛋白SMG5与肝癌临床病理及免疫浸润相关性分析

肝脏 ›› 2025, Vol. 30 ›› Issue (4): 435-440.

RNA结合蛋白SMG5与肝癌临床病理及免疫浸润相关性分析

张粉娜, 张心怡, 孙荣荣, 郝帅, 王辉, 贺娜, 钟岳

710077 陕西西安医学院第一附属医院 (张粉娜,张心怡,孙荣荣,郝帅,王辉,贺娜); 710021 陕西西安医学院(张心怡,孙荣荣,王辉); 710005 西安陕西省第二人民医院(钟岳)

收稿日期:2024-01-30 出版日期:2025-04-30 发布日期:2025-06-17
通讯作者: 钟岳,Email: zhongyue197906@163.com
基金资助:
陕西基础科学(化学、生物学)研究院基础科学研究计划(22JHQ091);陕西省自然科学基础研究计划(2021JM-493)

An analysis on the correlation between RNA binding protein SMG5 with clinicopathologies and immune infiltration in liver cancer

ZHANG Fen-na¹, ZHANG Xin-yi^1,2, SUN Rong-rong^1,2, HAO Shuai¹, WANG Hui^1,2, HE Na¹, ZHONG Yue³

1. The First Affiliated Hospital of Xi'an Medical University, Shaanxi 710077,China;
2. Xi'an Medical University, Shaanxi 710021,China;
3. Shaanxi Second Provincial People's Hospital, Xi'an 710005, China

Received:2024-01-30 Online:2025-04-30 Published:2025-06-17
Contact: ZHONG Yue, Email: zhongyue197906@163.com

摘要/Abstract

摘要： 目的探索RNA结合蛋白SMG5在肝癌中表达及其在临床诊断、预后的意义和生物学功能。方法 TCGA数据库下载肝癌测序数据和临床信息,R语言分析SMG5的表达、诊断价值及与临床信息之间的相关性,TNM plot芯片样本验证。Kaplan-Meier plot和TIMER 2.0分别分析SMG5表达与肝癌患者预后和肿瘤免疫浸润的相关性。UACLAN及cBioPortal分析SMG5甲基化及突变情况。STRING分析SMG5蛋白相互作用网络并进行功能富集。结果 SMG5在肝癌中显著上调(P=1.13×10^-26)且与肿瘤分级、AFP和ishak纤维化评分显著正相关(P=0.0014、7.26×10^-7和0.01),与肝癌患者5年总生存率和5年疾病特异性生存率显著负相关(P=6.4×10^-6和0.00028)。SMG5对于肝癌具有较高的诊断效果(AUC = 0.965)。SMG5与B细胞、CD4⁺T、巨噬细胞、髓系抑制性细胞等细胞浸润呈正相关(P=2.27×10^-6、2.05×10^-6、1.43×10^-6和2.64×10^-21),与肿瘤成纤维细胞、造血干细胞、内皮细胞等细胞浸润呈显著负相关关系(P=4.95×10^-3、8.08×10^-15和1.00×10^-17)。肝癌中SMG5的启动子甲基化显著低于对照组(P=6.91×10^-7),且cg10199857位点甲基化水平降低与患者不良预后密切相关(P=0.0035),S725C位点的突变与SMG5异常转录相关。SMG5与多个蛋白相互作用参与调控RNA代谢相关的生理活动。结论 SMG5在肝癌中显著上调且与患者的不良预后密切相关,可通过调控RNA代谢及转运等参与肝癌发展。同时,SMG5有较高的诊断价值,可作为肝癌诊断和预后评估的潜在标志物。

关键词: 肝癌, 肿瘤预后, SMG5, 标志物, 免疫浸润

Abstract: Objective To explore the expression and biofunction of RNA binding protein SMG5 in liver cancer (LC) and its significance in the diagnosis and prognostic prediction. Methods Liver cancer associated sequence data and clinic information were downloaded from TCGA database and analyzed by R to explore the expression, diagnosis value and clinical association of SMG5. Chip data of TNM plot was used for verification. Kaplan-Meier plot and TIMER 2.0 was used to assess the correlation between SMG5 and prognosis and tumor immune infiltration in liver cancer. UACLAN and cBioPortal were used for SMG5 methylation and mutation analyses. STRING was utilized for SMG5 associated protein interaction analyses, followed by GO and KEGG enrichment analysis. Results SMG5 was significantly upregulated in liver cancer (P=1.13×10^-26), and positively correlated with tumor grade, AFP, and ishak fibrosis score (P=0.0014, 7.26×10^-7 and 0.01), but negatively correlated with 5 year-overall survival rate and disease specific survival rate (P=6.4×10^-6 and 0.00028, respectively) of the patients. SMG5 presented a relative higher diagnostic value in liver cancer (AUC=0.965). SMG5 was positively correlated with the infiltration of B cell, CD4⁺T, macrophage, myeloid-derived suppressor cells (P=2.27×10^-6, 2.05×10^-6, 1.43×10^-6 and 2.64×10^-21), but negatively correlated with tumor associated fibroblasts, hematopoietic stem cells, endothelial cells (P=4.95×10^-3, 8.08×10^-15 and 1.00×10^-17). The methylation of SMG5 promoter in liver cancer was significantly lower than that in the control group (P=6.91×10^-7), downregulation of the methylation level of cg10199857 site was significantly correlated with a poor prognosis of the patients (P=0.0035), and S725C mutation was correlated with aberrant SMG5 transcription. SMG5 could interacted with several protein to regulate RNA metabolic associated process. Conclusion SMG5 was significantly upregulated in liver cancer and associated with the poor prognosis of patients. In addition, SMG5 presented high diagnostic value and could be used as an underlying biomarker for liver cancer.

Key words: Liver cancer, Tumor prognosis, SMG5, Biomarker, Immune infiltration

张粉娜, 张心怡, 孙荣荣, 郝帅, 王辉, 贺娜, 钟岳. RNA结合蛋白SMG5与肝癌临床病理及免疫浸润相关性分析[J]. 肝脏, 2025, 30(4): 435-440.

ZHANG Fen-na, ZHANG Xin-yi, SUN Rong-rong, HAO Shuai, WANG Hui, HE Na, ZHONG Yue. An analysis on the correlation between RNA binding protein SMG5 with clinicopathologies and immune infiltration in liver cancer[J]. Chinese Hepatolgy, 2025, 30(4): 435-440.

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