一个用于预测卵巢癌预后和评估肿瘤免疫微环境的新型相关于火凤凰死亡的特征标识。
A Novel pyroptosis-related signature for predicting prognosis and evaluating tumor immune microenvironment in ovarian cancer.
发表日期:2023 Sep 20
作者:
Jiani Yang, Chao Wang, Yue Zhang, Shanshan Cheng, Yanna Xu, Yu Wang
来源:
Journal of Ovarian Research
摘要:
卵巢癌(OV)是全球最致命的妇科恶性肿瘤,具有高复发率和极大的异质性。医疗发展中一种新认知的炎症型细胞死亡方式被称为火凤凰现象,对癌症进程有重要作用,尽管寻找卵巢癌中火凤凰现象的预后模型的研究还很缺乏。在我们的研究中,我们从376个TCGA-OV样本和180个正常对照中的6406个差异表达基因(DEGs)中筛选出了106个潜在的与火凤凰现象相关的基因(PRGs)。通过LASSO-Cox分析,最终确定了由CITED2、EXOC6B、MIA2、NRAS、SETBP1和TRPV46组成的六基因预后特征。然后,通过K-M生存分析和时间相关ROC曲线验证了六基因特征的良好预后价值(p值<0.0001)。此外,基于这一特征和相应的临床特征,我们构建并验证了1年、2年和3年的卵巢癌生存预测模型,在TCGA-OV(p值<0.001)和ICGC-OV队列(p值=0.040)中显示出可靠的预后价值。通过通路分析,我们发现了一些与火凤凰现象相关的关键通路;而基于m6A分析结果显示,高危组织中的m6A水平较高。我们使用CIBERSORT算法评估了肿瘤免疫微环境,结果显示高危组织中M1型巨噬细胞和激活的DC表达上调,并且关键免疫检查点分子(CTLA4、PDCD1LG2和HAVCR2)高表达。有趣的是,高危组织对免疫疗法的敏感性较差,但对紫杉醇、多西他赛和索拉非尼等化疗药物更为敏感。简言之,火凤凰现象相关特征是一种有前景的预测工具,可用于预测预后和评估免疫应答,从而辅助精准医学中的卵巢癌患者制定决策。© 2023年. BioMed Central Ltd., 为Springer Nature的一部分。
Ovarian cancer (OV) is the most fatal gynecological malignant tumor worldwide, with high recurrence rates and great heterogeneity. Pyroptosis is a newly-acknowledged inflammatory form of cell death with an essential role in cancer progression, though studies focusing on prognostic patterns of pyroptosis in OV are still lacking. Our research filtered 106 potential pyroptosis-related genes (PRGs) among the 6406 differentially expressed genes (DEGs) between the 376 TCGA-OV samples and 180 normal controls. Through the LASSO-Cox analysis, the 6-gene prognostic signature, namely CITED2, EXOC6B, MIA2, NRAS, SETBP1, and TRPV46, was finally distinguished. Then, the K-M survival analysis and time-dependent ROC curves demonstrated the promising prognostic value of the 6-gene signature (p-value < 0.0001). Furthermore, based on the signature and corresponding clinical features, we constructed and validated a nomogram model for 1-year, 2-year, and 3-year OV survival, with reliable prognostic values in TCGA-OV (p-value < 0.001) and ICGC-OV cohort (p-value = 0.040). Pathway analysis enriched several critical pathways in cancer, refer to the pyroptosis-related signature, while the m6A analysis indicated greater m6A level in high-risk group. We assessed tumor immune microenvironment through the CIBERSORT algorithm, which demonstrated the upregulation of M1 Macrophages and activated DCs and high expression of key immune checkpoint molecules (CTLA4, PDCD1LG2, and HAVCR2) in high-risk group. Interestingly, the high-risk group exhibited poor sensitivity towards immunotherapy and better sensitivity towards chemotherapies, including Vinblastine, Docetaxel, and Sorafenib. Briefly, the pyroptosis-related signature was a promising tool to predict prognosis and evaluate immune responses, in order to assist decision-making for OV patients in the realm of precision medicine.© 2023. BioMed Central Ltd., part of Springer Nature.