School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Clinical Laboratory Center, Shaoxing People's Hospital (Shaoxing Hospital), Shaoxing, Zhejiang, China.
Cancer Med. 2024 Aug;13(15):e70090. doi: 10.1002/cam4.70090.
Non-small-cell lung cancer (NSCLC) often presents at later stages, typically associated with poor prognosis. Autophagy genes play a role in the progression of tumors. This study investigated the clinical relevance, prognostic value, and biological significance of RBBP4 in NSCLC.
We assessed RBBP4 expression using the GSE30219 and TCGA NSCLC datasets and NSCLC cells, exploring its links with clinical outcomes, tumor immunity, and autophagy genes through bioinformatics analysis after transcriptome sequencing of RBBP4-knockdown and control PC9 cells. We identified differentially expressed genes (DEGs) and conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and protein-protein interaction network analyses. The significance of autophagy-related DEGs was evaluated for diagnosis and prognosis using the GSE30219 dataset. Experiments both in vivo and in vitro explored the biological mechanisms behind RBBP4-mediated autophagic cell death in NSCLC.
RBBP4 overexpression in NSCLC correlates with a poorer prognosis. Eighteen types of immune cell were significantly enriched in cultures that had low RBBP4 expression compared high expression. DEGs associated with RBBP4 are enriched in autophagy pathways. Transcriptomic profiling of the PC9 cell line identified autophagy-related DEGs associated with RBBP4 that exhibited differential expression in NSCLC, suggesting prognostic applications. In vitro experiments demonstrated that RBBP4 knockdown induced autophagy and apoptosis in PC9 cells, promoting cell death, which was inhibited by 3-MA. In vivo, targeted siRNA against RBBP4 significantly reduced tumor development in PC9 cell-injected nude mice, elevating autophagy-related protein levels and inducing apoptosis and necrosis in tumor tissues.
In NSCLC, RBBP4 upregulation correlates with poor prognosis and altered immunity. Its knockdown induces autophagic cell death in NSCLC cells. These results indicate RBBP4 as a potential NSCLC diagnostic marker and its autophagy modulation as a prospective therapeutic target.
非小细胞肺癌（NSCLC）常发生于晚期，预后通常较差。自噬基因在肿瘤进展中发挥作用。本研究旨在探讨 RBBP4 在 NSCLC 中的临床相关性、预后价值和生物学意义。
我们使用 GSE30219 和 TCGA NSCLC 数据集以及 NSCLC 细胞评估 RBBP4 的表达，通过转录组测序敲低和对照 PC9 细胞的生物信息学分析，探讨 RBBP4 与临床结局、肿瘤免疫和自噬基因的关系。我们鉴定了差异表达基因（DEGs），并进行了基因本体论、京都基因与基因组百科全书通路富集以及蛋白质-蛋白质相互作用网络分析。使用 GSE30219 数据集评估自噬相关 DEGs 对 NSCLC 的诊断和预后的意义。体内和体外实验均探索了 RBBP4 介导的 NSCLC 自噬性细胞死亡的生物学机制。
NSCLC 中 RBBP4 的过表达与预后较差相关。与高表达相比，低表达 RBBP4 的培养物中明显富集了 18 种免疫细胞。与 RBBP4 相关的 DEGs 富集在自噬途径中。PC9 细胞系的转录组分析鉴定了与 RBBP4 相关的自噬相关 DEGs，这些基因在 NSCLC 中表现出差异表达，提示具有预后应用价值。体外实验表明，PC9 细胞中 RBBP4 敲低诱导自噬和细胞凋亡，促进细胞死亡，而 3-MA 可抑制该过程。体内实验中，针对 RBBP4 的靶向 siRNA 显著减少了 PC9 细胞注射裸鼠中的肿瘤发展，提高了肿瘤组织中自噬相关蛋白的水平，并诱导了凋亡和坏死。
在 NSCLC 中，RBBP4 的上调与不良预后和免疫改变相关。敲低 RBBP4 可诱导 NSCLC 细胞发生自噬性细胞死亡。这些结果表明 RBBP4 可作为 NSCLC 的潜在诊断标志物，其自噬调节可能成为有前景的治疗靶点。
