对RNASET2基因在清晰细胞肾细胞癌中作为潜在预后和免疫学生物标志物的系统分析。
Systematic analysis of RNASET2 gene as a potential prognostic and immunological biomarker in clear cell renal cell carcinoma.
发表日期:2023 Sep 07
作者:
Yifu Liu, Zhicheng Zhang, Ping Xi, Ru Chen, Xiaofeng Cheng, Ji Liu, Qiqi Zhu, Yechen Nie, Ting Sun, Binbin Gong, Siyuan Wang
来源:
Immunity & Ageing
摘要:
RNASET2已被确定为一个具有抗血管生成和免疫调节作用的癌基因,在各种癌症中都有作用,但其在透明细胞肾细胞癌(ccRCC)中的功能尚不明确。RNASET2表达矩阵从癌症基因组图谱(TCGA)和基因表达数据库(GEO)数据集中提取,并进行了诊断和预后价值分析。采用定量聚合酶链反应(qPCR)检测ccRCC患者和肾癌细胞株中的RNASET2 mRNA表达。采用划痕愈合实验、Transwell实验、Western blotting和管形成实验评估RNASET2在肾癌体外的功能。此外,对沉默RNASET2的肾癌细胞进行转录组测序,分析其可能的信号通路。此外,评估免疫微环境和突变状态以预测RNASET2参与肾癌进展的潜在机制。根据癌症药物敏感性基因组学(GDSC)数据库评估常见化疗药物和靶向药物的敏感性。RNASET2在ccRCC组织和肾癌细胞株中显著上调,预示着患者预后差。体外实验表明,沉默RNASET2抑制了肾癌细胞的迁移和促血管生成能力。转录组测序表明其可能参与肾细胞癌免疫微环境的重塑。此外,生物信息学分析和免疫组化染色结果表明RNASET2与调节性T细胞渗透丰度呈正相关。最后,我们对ccRCC中RNASET2的突变图谱进行了绘制,并发现其对药物敏感性具有预测价值。我们的结果表明,RNASET2是ccRCC中有前景的生物标记和治疗靶点。© 2023. 白海鹰出版社有限公司,施普林格公司的组成部分。
RNASET2 has been identified as an oncogene with anti-angiogenic and immunomodulatory effects in a variety of cancers, but its function in clear cell renal cell carcinoma (ccRCC) is still not well understood.The RNASET2 expression matrix was extracted from the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and analyzed for diagnostic and prognostic value. RNASET2 mRNA expression was detected by quantitative polymerase chain reaction (qPCR) in ccRCC patients and renal cancer cell lines. Wound healing assay, transwell assay, western blotting, and tube formation assays were used to evaluate the function of RNASET2 in renal cancer in vitro. In addition, transcriptome sequencing was performed on knockdown RNASET2 kidney cancer cells to analyze their potential signaling pathways. Moreover, the immune microenvironment and mutational status were evaluated to predict the potential mechanisms of RNASET2 involvement in renal cancer progression. Sensitivity to common chemotherapeutic and targeted agents was assessed according to the Genomics of Drug Sensitivity in Cancer (GDSC) database.RNASET2 expression was significantly upregulated in ccRCC tissues and renal cancer cell lines, predicting poor prognosis for patients. In vitro experiments showed that silencing RNASET2 inhibited the migration and pro-angiogenic ability of renal cancer cells. Transcriptome sequencing suggested its possible involvement in the remodeling of the immune microenvironment in renal cell carcinoma. Furthermore, bioinformatics analysis and immunohistochemical staining showed that RNASET2 was positively correlated with the infiltration abundance of regulatory T cells. Finally, we mapped the mutational landscape of RNASET2 in ccRCC and found its predictive value for drug sensitivity.Our results suggest that RNASET2 is a promising biomarker and therapeutic target in ccRCC.© 2023. BioMed Central Ltd., part of Springer Nature.