Li Fu-Ping, Liu Gao-Hua, Zhang Xue-Qin, Kong Wei-Jie, Mei Jian, Wang Mao, Dai Yin-Hai
Department of Clinical Medicine, Shaanxi University of Chinese Medicine Xianyang 712046, Shaanxi, China.
Department of Oncology, Fujian Medical University Union Hospital Fuzhou 350001, Fujian, China.
Am J Transl Res. 2022 Jun 15;14(6):4207-4228. eCollection 2022.
Prior reports have indicated that the abnormal expression of small nuclear ribonucleoproteins (snRNPs) genes is related to malignant tumors. However, in hepatocellular carcinoma (HCC), the precise role of snRNPs is not well understood. Therefore, the purpose of this study was to evaluate the prognostic roles of SNRPB/D1/D2/D3/E/F/G and their correlation to immune infiltration in HCC.
The study was carried out via the following databases, software, and experimental validation: ONCOMINE, GEPIA2, UALCAN, The Cancer Genome Atlas, Gene Expression Omnibus, ArrayExpress, Kaplan-Meier plotter, cBioPortal, STRING, DAVID 6.8, TIMER, Cytoscape software, and immunohistochemistry experiments.
Overexpressed SNRPB/D1/D2/D3/E/F/G proteins were found in HCC tissues. The transcription levels of 7 snRNPs genes were related to the TP53 mutation and tumor grades. SNRPB/D1/D2/D3/F/G expression was significantly correlated with cancer staging, whereas SNRPE was not. Moreover, Kaplan-Meier survival analysis showed that upregulation of SNRPB/D1/D2/E/G was relevant to worse OS in HCC patients, especially in patients with alcohol consumption and those without viral hepatitis. Multivariate Cox regression analysis indicated that expression of SNRPB/D1/D3/E/F/G were independent prognostic factors for unfavorable OS in HCC. In addition, a high mutation rate of snRNPs genes (44%) was also found in HCC. The mRNA expression levels of snRNPs were meaningfully and positively related to six types of infiltrating immune cells (B cells, CD4 T cells, CD8 T cells, neutrophil, macrophage, and dendritic cells). Also, SNRPB/D1/G genes were significantly associated with molecular markers of various immune cells in HCC.
SNRPB/D1/D3/E/F/G are potential prognostic biomarkers for a short OS in HCC, and SNRPB/D1/G were novel immune therapy targets in HCC patients.
先前的报道表明，小核核糖核蛋白（snRNPs）基因的异常表达与恶性肿瘤有关。然而，在肝细胞癌（HCC）中，snRNPs的确切作用尚不清楚。因此，本研究的目的是评估SNRPB/D1/D2/D3/E/F/G在HCC中的预后作用及其与免疫浸润的相关性。
本研究通过以下数据库、软件和实验验证进行：ONCOMINE、GEPIA2、UALCAN、癌症基因组图谱、基因表达综合数据库、ArrayExpress、Kaplan-Meier绘图仪、cBioPortal、STRING、DAVID 6.8、TIMER、Cytoscape软件和免疫组织化学实验。
在HCC组织中发现SNRPB/D1/D2/D3/E/F/G蛋白过表达。7个snRNPs基因的转录水平与TP53突变和肿瘤分级有关。SNRPB/D1/D2/D3/F/G的表达与癌症分期显著相关，而SNRPE则不然。此外，Kaplan-Meier生存分析表明，SNRPB/D1/D2/E/G的上调与HCC患者较差的总生存期相关，尤其是在饮酒患者和无病毒性肝炎患者中。多变量Cox回归分析表明，SNRPB/D1/D3/E/F/G的表达是HCC患者总生存期不良的独立预后因素。此外，在HCC中还发现snRNPs基因的高突变率（44%）。snRNPs的mRNA表达水平与六种浸润性免疫细胞（B细胞、CD4 T细胞、CD8 T细胞、中性粒细胞、巨噬细胞和树突状细胞）有显著的正相关。此外，SNRPB/D1/G基因与HCC中各种免疫细胞的分子标记物显著相关。
SNRPB/D1/D3/E/F/G是HCC患者总生存期短的潜在预后生物标志物，SNRPB/D1/G是HCC患者新的免疫治疗靶点。
