前列腺癌中昼夜节律时钟相关免疫预后指数及分子亚型的鉴定
Identification of circadian clock-related immunological prognostic index and molecular subtypes in prostate cancer.
作者信息
Che Lu, Li Dengxiong, Wang Jie, Tuo Zhouting, Yoo Koo Han, Feng Dechao, Ou Yun, Wu Ruicheng, Wei Wuran
机构信息
Operating Room, Department of Anesthesiology, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, 610041, China.
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
出版信息
Discov Oncol. 2024 Sep 11;15(1):429. doi: 10.1007/s12672-024-01276-7.
BACKGROUND
Evidence suggests that the circadian clock (CIC) is among the important factors for tumorigenesis. We aimed to provide new insights into CIC-mediated molecular subtypes and gene prognostic indexes for prostate cancer (PCa) patients undergoing radical prostatectomy (RP) or radical radiotherapy (RT).
METHODS
PCa data from TCGA was analyzed to identify differentially expressed genes (DEGs) with significant fold changes and p-values. A prognostic index called CIC-related gene prognostic index (CICGPI) was developed through clustering methods and survival analysis and validated on multiple data sets. The diagnostic accuracy of CICGPI for resistance to chemotherapy and radiotherapy was confirmed. Additionally, the interaction between tumor immune environment and CICGPI score was explored, along with their correlation with prognosis.
RESULTS
TOP2A, APOE, and ALDH2 were used to classify the PCa patients into two subtypes. Cluster 2 had a higher risk of biochemical recurrence (BCR) than cluster 1 for PCa patients undergoing RP or RT. A CIC-related gene prognostic index (CICGPI) was constructed using the above three genes for PCa patents in the TCGA database. The CICGPI score showed good prognostic value in the TCGA database and was externally confirmed by PCa patients in GSE116918, MSKCC2010 and GSE46602. In addition, the CICGPI score had a certain and high diagnostic accuracy for tumor chemoresistance (AUC: 0.781) and radioresistance (AUC: 0.988). For gene set variation analysis, we observed that both beta alanine metabolism and limonene and pinene degradation were upregulated in cluster 1 for PCa patients undergoing RP or RT. For PCa patients undergoing RP, cell cycle, homologous recombination, mismatch repair, and DNA replication were upregulated in cluster 2. A strongly positive relationship between cancer-related fibroblasts and CICGPI score was observed in PCa patients undergoing RP or RT. Moreover, a high density of CAFs was highly closely associated with poorer BCR-free survival of PCa patients.
CONCLUSIONS
In this study, we established CIC-related immunological prognostic index and molecular subtypes, which might be useful for the clinical practice.
背景
有证据表明，昼夜节律时钟（CIC）是肿瘤发生的重要因素之一。我们旨在为接受根治性前列腺切除术（RP）或根治性放疗（RT）的前列腺癌（PCa）患者的CIC介导的分子亚型和基因预后指标提供新的见解。
方法
分析来自TCGA的PCa数据，以识别具有显著倍数变化和p值的差异表达基因（DEG）。通过聚类方法和生存分析开发了一种名为CIC相关基因预后指数（CICGPI）的预后指标，并在多个数据集上进行了验证。证实了CICGPI对化疗和放疗耐药性的诊断准确性。此外，还探讨了肿瘤免疫环境与CICGPI评分之间的相互作用，以及它们与预后的相关性。
结果
使用TOP2A、APOE和ALDH2将PCa患者分为两个亚型。对于接受RP或RT的PCa患者，聚类2的生化复发（BCR）风险高于聚类1。使用上述三个基因构建了TCGA数据库中PCa患者的CIC相关基因预后指数（CICGPI）。CICGPI评分在TCGA数据库中显示出良好的预后价值，并在GSE116918、MSKCC2010和GSE46602中的PCa患者中得到外部验证。此外，CICGPI评分对肿瘤化疗耐药性（AUC：0.781）和放疗耐药性（AUC：0.988）具有一定且较高的诊断准确性。对于基因集变异分析，我们观察到对于接受RP或RT的PCa患者，聚类1中的β-丙氨酸代谢以及苎烯和蒎烯降解均上调。对于接受RP的PCa患者，聚类2中的细胞周期、同源重组、错配修复和DNA复制上调。在接受RP或RT的PCa患者中，观察到癌症相关成纤维细胞与CICGPI评分之间存在强正相关。此外，高密度的CAFs与PCa患者较差的无BCR生存率高度密切相关。
结论
在本研究中，我们建立了CIC相关的免疫预后指标和分子亚型，这可能对临床实践有用。
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