程序性细胞死亡(PCD)是一个过程,消除感染,损坏,或者可能是肿瘤细胞来维持稳态多细胞生物。尽管长链非编码RNA(lncRNA)参与各种类型的PCD并调节肿瘤生长,入侵,和移民,PCD相关lncRNAs在膀胱癌中的作用仍缺乏系统的探索.在这项研究中,我们整合了多种类型的PCD为泛PCD,并鉴定了八个泛PCD相关的lncRNAs(LINC00174,HCP5,HCG27,UCA1,SNHG15,GHRLOS,CYB561D2和AGAP11)。然后,我们生成了一个pan-PCD相关的lncRNA预后特征(PPlncPS),具有出色的预测能力和可靠性,在E-MTAB-4321队列中表现同样良好。与低PPlncPS评分组相比,高PPlncPS评分组的血管生成水平明显较高,矩阵,癌症相关成纤维细胞,骨髓细胞交通,和质子细胞因子签名。此外,低PPlncPS评分组与相对丰富的免疫细胞浸润呈正相关,上调免疫检查点的表达水平,和高肿瘤突变负荷(TMB)。免疫基因组谱显示,低PPlncPS评分和高TMB的患者预后最好,可能受益于免疫检查点抑制剂。此外,对于PPlncPS评分高的患者,多西他赛,星形孢菌素,和luminespib被筛选为潜在的治疗候选人。总之,我们产生了一个泛PCD相关的lncRNA签名,为临床预后提供精确和个性化的预测,并为膀胱癌的化疗和免疫检查点抑制剂治疗提供一些新的见解。
Programmed cell death (PCD) is a process that eliminates infected, damaged, or possibly neoplastic cells to sustain homeostatic multicellular organisms. Although long noncoding RNAs (lncRNAs) are involved in various types of PCD and regulate tumor growth, invasion, and migration, the role of PCD-related lncRNAs in bladder cancer still lacks systematic exploration. In this research, we integrated multiple types of PCD as pan-PCD and identified eight pan-PCD-related lncRNAs (LINC00174, HCP5, HCG27, UCA1, SNHG15, GHRLOS, CYB561D2, and AGAP11). Then, we generated a pan-PCD-related lncRNA prognostic
signature (PPlncPS) with excellent predictive power and reliability, which performed equally well in the E-MTAB-4321 cohort. In comparison with the low-PPlncPS score group, the high-PPlncPS score group had remarkably higher levels of angiogenesis, matrix, cancer-associated fibroblasts, myeloid cell traffic, and protumor cytokine signatures. In addition, the low-PPlncPS score group was positively correlated with relatively abundant immune cell infiltration, upregulated expression levels of immune checkpoints, and high tumor mutation burden (TMB). Immunogenomic profiles revealed that patients with both low PPlncPS scores and high TMB had the best prognosis and may benefit from immune checkpoint inhibitors. Furthermore, for patients with high PPlncPS scores, docetaxel, staurosporine, and luminespib were screened as potential therapeutic candidates. In conclusion, we generated a pan-PCD-related lncRNA
signature, providing precise and individualized prediction for clinical prognosis and some new insights into chemotherapy and immune checkpoint inhibitor therapy for bladder cancer.