■铁凋亡,作为一种新的程序性细胞死亡形式,在膀胱癌的发生、发展中起着至关重要的作用。然而,BCa的肿瘤微环境(TME)中铁凋亡的调节机制仍有待阐明。
■基于BCa的单细胞RNA(scRNA)转录组数据,我们采用非负矩阵分解(NMF)降维聚类来识别BCaTME内的新型铁凋亡相关细胞亚型,目的探讨这些TME细胞亚型的生物学特性。随后,我们进行了生存分析和单因素Cox回归分析,以探讨这些细胞亚型的预后意义.我们调查了特定亚型与免疫浸润之间的关系,以及它们对免疫疗法的影响。最后,我们发现了一种有价值的新型生物标志物,由一系列体外实验支持。
■我们细分了癌症相关成纤维细胞(CAFs),巨噬细胞,并通过NMF将T细胞分为3-5个小亚群,并进一步探索其生物学特性。我们发现铁性凋亡在BCaTME中起重要作用。通过大量RNA-seq分析,我们进一步验证了铁性凋亡会影响进展,预后,和通过调节TME对BCa的免疫治疗反应。尤其是ACSL4+CAF,我们发现,这种CAF亚型的高水平浸润预示着更差的预后,更复杂的免疫浸润,免疫疗法的反应较少。此外,我们发现这种类型的CAF通过PTN-SDC1轴与癌细胞相关,这表明SDC1可能在调节癌细胞中的CAFs中至关重要。一系列体外实验证实了这些推论:SDC1促进了BCa的进展。有趣的是,我们还发现了FTH1+巨噬细胞,与SPP1+巨噬细胞密切相关,也可能参与BCaTME的调节。
■这项研究揭示了铁凋亡对膀胱癌TME的显着影响,并鉴定了新的铁凋亡相关的TME细胞亚群,ACSL4+CAF,和重要的BCa生物标志物SDC1。
UNASSIGNED: Ferroptosis, as a novel form of programmed cell death, plays a crucial role in the occurrence and development of bladder cancer (BCa). However, the regulatory mechanisms of ferroptosis in the tumor microenvironment (TME) of BCa remain to be elucidated.
UNASSIGNED: Based on single-cell RNA (scRNA) transcriptomic data of BCa, we employed non-negative matrix factorization (NMF) dimensionality reduction clustering to identify novel ferroptosis-related cell subtypes within the BCa TME, aiming to explore the biological characteristics of these TME cell subtypes. Subsequently, we conducted survival analysis and univariate Cox regression analysis to explore the prognostic significance of these cell subtypes. We investigated the relationship between specific subtypes and immune infiltration, as well as their implications for immunotherapy. Finally, we discovered a valuable and novel biomarker for BCa, supported by a series of in vitro experiments.
UNASSIGNED: We subdivided cancer-associated fibroblasts (CAFs), macrophages, and T cells into 3-5 small subpopulations through NMF and further explored the biological features. We found that ferroptosis played an important role in the BCa TME. Through bulk RNA-seq analysis, we further verified that ferroptosis affected the progression, prognosis, and immunotherapy response of BCa by regulating the TME. Especially ACSL4+CAFs, we found that high-level infiltration of this CAF subtype predicted worse prognosis, more complex immune infiltration, and less response for immunotherapy. Additionally, we found that this type of CAF was associated with cancer cells through the PTN-SDC1 axis, suggesting that SDC1 may be crucial in regulating CAFs in cancer cells. A series of in vitro experiments confirmed these inferences: SDC1 promoted the progression of BCa. Interestingly, we also discovered FTH1+ macrophages, which were closely related to SPP1+ macrophages and may also be involved in the regulation of BCa TME.
UNASSIGNED: This study revealed the significant impact of ferroptosis on bladder cancer TME and identified novel ferroptosis-related TME cell subpopulations, ACSL4+CAFs, and important BCa biomarker SDC1.