Department of Urology, Changhai Hospital, Naval Medical University (Second Military Medical University), Shanghai, China.
Department of Urology, The First Affiliated Hospital of Anhui Medical University; Institute of Urology, Anhui Medical University; Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, China.
Front Immunol. 2022 Feb 23;13:842069. doi: 10.3389/fimmu.2022.842069. eCollection 2022.
Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma and is associated with poor prognosis and notorious for its immune dysfunction characteristic. SNRPA1 is a spliceosome component responsible for processing pre-mRNA into mRNA, while the biological effect of SNRPA1 in ccRCC remains elusive. The aim of this study was to decipher the effect of SNRPA1 on clinical effect and tumor immunity for ccRCC patients. Multi-databases were collected to evaluate the different expression, prognostic value, DNA methylation, tumor immune microenvironment, and drug sensitivity of SNRPA1 on ccRCC. IHC was utilized to validate the expression and prognostic value of SNRPA1 in ccRCC patients from the SMMU cohort. The knockout expression of SNRPA by sgRNA plasmid inhibited the cell proliferation, migration, and metastasis ability and significantly increased the sensitivity of sunitinib treatment. In addition, we explored the role of SNRPA1 in pan-cancer level. The results indicated that SNRPA1 was differentially expressed in most cancer types. SNRPA1 may significantly influence the prognosis of multiple cancer types, especially in ccRCC patients. Notably, SNRPA1 was significantly correlated with immune cell infiltration and immune checkpoint inhibitory genes. In addition, the aggressive and immune inhibitory effects shown in SNRPA1 overexpression and the effect of SNRPA1 on ccRCC cell line invasion, metastasis, and drug sensitivity were observed. Moreover, SNRPA1 was related to Myc, MTORC, G2M, E2F, and DNA repair pathways in various cancer types. In all, SNRPA1 may prove to be a new biomarker for prognostic prediction, effect tumor immunity, and drug susceptibility in ccRCC.
透明细胞肾细胞癌(ccRCC)是最常见的肾细胞癌亚型,与预后不良有关,其免疫功能障碍特征尤为明显。SNRPA1 是一种剪接体成分,负责将前体 mRNA 加工成成熟的 mRNA,而 SNRPA1 在 ccRCC 中的生物学效应尚不清楚。本研究旨在阐明 SNRPA1 对 ccRCC 患者临床疗效和肿瘤免疫的影响。本研究通过多数据库评估 SNRPA1 在 ccRCC 中的不同表达、预后价值、DNA 甲基化、肿瘤免疫微环境和药物敏感性。通过免疫组织化学(IHC)验证了 SNRPA1 在 SMMU 队列 ccRCC 患者中的表达和预后价值。通过 sgRNA 质粒敲除 SNRPA1 的表达,抑制了细胞增殖、迁移和转移能力,并显著提高了舒尼替尼治疗的敏感性。此外,我们还在泛癌水平上探讨了 SNRPA1 的作用。结果表明,SNRPA1 在大多数癌症类型中存在差异表达。SNRPA1 可能显著影响多种癌症类型的预后,尤其是 ccRCC 患者。值得注意的是,SNRPA1 与免疫细胞浸润和免疫检查点抑制基因显著相关。此外,在 SNRPA1 过表达时观察到的侵袭、转移和药物敏感性的作用与 SNRPA1 对 ccRCC 细胞系的侵袭、转移和药物敏感性的作用相似。此外,在各种癌症类型中,SNRPA1 与 Myc、MTORC、G2M、E2F 和 DNA 修复途径有关。总之,SNRPA1 可能成为预测预后、影响肿瘤免疫和药物敏感性的新的生物标志物。