目的:前列腺癌(PCa)是全球威胁男性健康的主要肿瘤疾病之一,生化复发显著影响其预后。二硫化物下垂,最近发现的细胞死亡机制由细胞内二硫键积累引发,导致膜破裂,是PCa背景下的一个新的研究领域。目前,其对PCa的影响在很大程度上仍未被探索。本研究旨在探讨长链非编码RNA(lncRNA)与PCa预后的相关性。寻找两者之间的潜在联系。
方法:从癌症基因组图谱数据库获得PCa组群的转录组数据。通过差异表达和Pearson相关分析鉴定了二硫细胞凋亡相关lncRNAs(DDRLs)。使用单变量Cox和LASSO回归精确鉴定与生化无复发生存期(BRFS)相关的DDRL,从而开发了风险评分模型。通过单变量和多变量Cox分析确定与BRFS相关的临床因素。预后列线图将风险评分与关键临床变量相结合。使用接收器工作特性(ROC)曲线评估模型性能,决策曲线分析(DCA)和校准曲线。通过涉及CCK8,入侵,迁移,细胞克隆此外,对二硫键下垂相关蛋白SLC7A11进行免疫组织化学(IHC)染色。
结果:预后特征包括AC026401.3、SNHG4、SNHG25和U73166.1作为关键成分。从这些特征中得出的风险评分是PCa患者的独立预后因素之一。与高风险组中较差的BRFS相关。通过将风险评分与临床变量相结合,创建了一个实用的列线图,准确预测PCa患者的BRFS。值得注意的是,沉默AC026401.3显著阻碍PCa细胞增殖,入侵,迁移,和殖民地的形成。IHC染色显示,肿瘤组织中二硫代硫酸盐相关蛋白SLC7A11的表达升高。
结论:PCaDDRLs的新预后特征,拥有值得赞扬的预测能力,已经建造,同时提供与二硫键下垂相关的潜在治疗靶点,其中AC026401.3已在体外进行了验证,并证明其沉默后抑制了PCa的肿瘤发生。
OBJECTIVE: Prostate cancer (PCa) is one of the major tumor diseases that threaten men\'s health globally, and biochemical recurrence significantly impacts its prognosis. Disulfidptosis, a recently discovered cell death mechanism triggered by intracellular disulfide accumulation leading to membrane rupture, is a new area of research in the context of PCa. Currently, its impact on PCa remains largely unexplored. This study aims to investigate the correlation between long non-coding RNAs (lncRNAs) associated with disulfidptosis and the prognosis of PCa, seeking potential connections between the two.
METHODS: Transcriptomic data for a PCa cohort were obtained from the Cancer Genome Atlas database. Disulfidptosis-related lncRNAs (DDRLs) were identified through differential expression and Pearson correlation analysis. DDRLs associated with biochemical recurrence-free survival (BRFS) were precisely identified using univariate Cox and LASSO regression, resulting in the development of a risk score model. Clinical factors linked to BRFS were determined through both univariate and multivariate Cox analyses. A prognostic nomogram combined the risk score with key clinical variables. Model performance was assessed using Receiver Operating Characteristic (ROC) curves, Decision Curve Analysis (DCA), and calibration curves. The functional impact of a critical DDRL was substantiated through assays involving CCK8, invasion, migration, and cell cloning. Additionally, immunohistochemical (IHC) staining for the disulfidptosis-related protein SLC7A11 was conducted.
RESULTS: The prognostic signature included AC026401.3, SNHG4, SNHG25, and U73166.1 as key components. The derived risk score from these signatures stood as one of the independent prognostic factor for PCa patients, correlating with poorer BRFS in the high-risk group. By combining the risk score with clinical variables, a practical nomogram was created, accurately predicting BRFS of PCa patients. Notably, silencing AC026401.3 significantly hindered PCa cell proliferation, invasion, migration, and colony formation. IHC staining revealed elevated expression of the dithiosulfatide-related protein SLC7A11 in tumor tissue.
CONCLUSIONS: A novel prognostic signature for PCa DDRLs, possessing commendable predictive power, has been constructed, simultaneously providing potential therapeutic targets associated with disulfidptosis, among which AC026401.3 has been validated in vitro and demonstrated inhibition of PCa tumorigenesis after its silencing.