将CDCA3确定为预测泛肾细胞癌结果和免疫治疗疗效的关键生物标志物。
Identifying CDCA3 as a pivotal biomarker for predicting outcomes and immunotherapy efficacy in pan-renal cell carcinoma.
发表日期:2024 Sep 30
作者:
Hongwei Luo, Huichan He, Zezhen Liu, Yuting Liu, Feifei Hou, Yao Xie, Le Zhang, Jianming Lu, Shan Tang, Weide Zhong
来源:
Cell Death & Disease
摘要:
肾细胞癌(RCC)是一种异质性疾病。识别有效的生物标志物对于提高预后准确性和治疗结果至关重要。本研究探讨细胞分裂周期相关 3 (CDCA3) 作为 RCC 预后评估和免疫治疗反应的新型生物标志物。本研究分析了癌症基因组图谱 (TCGA) 中肾透明细胞癌 (KIRC) 的多组学数据,肾乳头状细胞癌 (KIRP) 和肾嫌色细胞 (KICH) 亚型,以评估 CDCA3 表达及其临床意义。使用生物信息学工具基因集富集分析 (GSEA) 和 xCell 进行功能富集和免疫浸润分析。通过 Cox 回归和 Kaplan-Meier 生存分析评估 CDCA3 的预后价值。采用免疫组织化学 (IHC) 来确认 RCC 样本中蛋白质水平的 CDCA3 表达。较高的 CDCA3 表达与较差的生存结果以及对程序性细胞死亡蛋白 1 (PD-1) 阻断疗法的反应降低相关。统计分析表明CDCA3是肾细胞癌生存不良的独立预后因素。与正常组织相比,CDCA3 在 RCC 组织中持续过度表达,并与不良临床特征相关,包括高 Th2 细胞浸润和免疫途径抑制。CDCA3 是 RCC 的一种有前途的生物标志物,可以深入了解肿瘤的预后和对免疫治疗的潜在反应。 CDCA3 表达与不良治疗结果之间的密切关联表明,CDCA3 可以成为未来治疗策略的目标。2024 AME 出版公司。版权所有。
Renal cell carcinoma (RCC) is a heterogeneous disease. Identifying effective biomarkers is crucial for improving prognostic accuracy and therapy outcomes. This study investigates cell division cycle-associated 3 (CDCA3) as a novel biomarker for prognostic assessment and immunotherapy response in RCC.This study analyzed multi-omics data from The Cancer Genome Atlas (TCGA) for kidney renal clear cell carcinoma (KIRC), kidney renal papillary cell carcinoma (KIRP), and kidney chromophobe (KICH) subtypes to evaluate CDCA3 expression and its clinical implications. Functional enrichment and immune infiltration analyses were performed using bioinformatics tools gene set enrichment analysis (GSEA) and xCell. The prognostic value of CDCA3 was assessed through Cox regression and Kaplan-Meier survival analysis. Immunohistochemistry (IHC) was employed to confirm CDCA3 expression at the protein level in RCC samples.Higher CDCA3 expression correlated with poor survival outcomes and reduced response to programmed cell death protein 1 (PD-1) blockade therapies. Statistical analysis indicated that CDCA3 was an independent prognostic factor for poor survival in RCC. CDCA3 was consistently overexpressed in RCC tissues compared to normal tissues and was associated with adverse clinical features, including high Th2 cell infiltration and suppression of immune pathways.CDCA3 is a promising biomarker for RCC, offering insights into the tumor's prognosis and potential response to immunotherapy. The strong association between CDCA3 expression and poor therapeutic outcomes suggests that CDCA3 could be targeted in future therapeutic strategies.2024 AME Publishing Company. All rights reserved.