Gu Yinfeng, Li Jinjin, Guan Hongjun, Sun Changpeng
Department of Thoracic Surgery, Jianhu People's Hospital, Yancheng, Jiangsu, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
J Chemother. 2024 Nov;36(7):566-579. doi: 10.1080/1120009X.2023.2298153. Epub 2023 Dec 26.
This article aimed to investigate the correlations among SKA3 expression and prognosis, clinical relevance, tumor immunity, and RNA-binding protein (RBP)-involved mechanisms for overall survival (OS) in lung adenocarcinoma (LUAD). To explore the SKA3 expression level in LUAD by analyzing the genomic data as well as related clinical characteristics from the database of TCGA. Nomogram and gene set enrichment analysis (GSEA) were applied, respectively, to evaluate the performance of SKA3 in LUAD. Correlations between SKA3 and immunity and RBP-involved mechanisms were also performed. SKA3 had a higher expression level in LUAD samples than in adjacent normal lung samples, with shorter survival times in the high-SKA3-expressed LUAD subgroup (P < 0.05). qRT-PCR results remained consistent (P < 0.05). Uni-/multivariate Cox analyses revealed that SKA3 could have independent prognostic ability for LUAD (both P < 0.05). The nomogram model constructed with clinical pathological parameters and SKA3 expression levels predicted OS rates for LUAD and GSEA revealed SKA3-related pathways. In aspects of tumor immunity, SKA3 was significantly involved with tumor neoantigen burden, tumor mutational burden, immune cell pathways, and immune checkpoint inhibitor (ICI) molecules (all P < 0.05). The CellMiner database also found significant correlations between SKA3 and the antitumor drug sensitivity of chemotherapy, fenretinide, and PX-316. Besides, a total of nine LncRNA/RBP/SKA3 networks were revealed in LUAD for their RBP-involved mechanisms. SKA3 could serve as a potential biomarker for OS prognosis and immunotherapy in LUAD. LncRNA/RBP/SKA3 networks were identified in LUAD for their RBP-involved mechanisms, paving the way for further experimental verifications.
本文旨在研究肺腺癌（LUAD）中SKA3表达与预后、临床相关性、肿瘤免疫以及RNA结合蛋白（RBP）相关机制对总生存期（OS）的相关性。通过分析TCGA数据库中的基因组数据以及相关临床特征，探讨LUAD中SKA3的表达水平。分别应用列线图和基因集富集分析（GSEA）评估SKA3在LUAD中的表现。还进行了SKA3与免疫及RBP相关机制之间的相关性分析。LUAD样本中SKA3的表达水平高于相邻正常肺组织样本，高SKA3表达的LUAD亚组生存时间较短（P < 0.05）。qRT-PCR结果一致（P < 0.05）。单因素/多因素Cox分析显示，SKA3对LUAD具有独立的预后能力（均P < 0.05）。由临床病理参数和SKA3表达水平构建的列线图模型预测了LUAD的OS率，GSEA揭示了与SKA3相关的通路。在肿瘤免疫方面，SKA3与肿瘤新抗原负荷、肿瘤突变负荷、免疫细胞通路和免疫检查点抑制剂（ICI）分子显著相关（均P < 0.05）。CellMiner数据库还发现SKA3与化疗药物、芬维A酸和PX-316的抗肿瘤药物敏感性之间存在显著相关性。此外，在LUAD中总共揭示了9个lncRNA/RBP/SKA3网络的RBP相关机制。SKA3可作为LUAD中OS预后和免疫治疗的潜在生物标志物。在LUAD中鉴定出lncRNA/RBP/SKA3网络的RBP相关机制，为进一步的实验验证铺平了道路。
