Yao Jiaxi, Liu Yue, Yang Jitao, Li Mengling, Li Simin, Zhang Bo, Yang Rui, Zhang Yuchong, Cui Xiaoyu, Feng ChunQing
Department of Urology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.
Front Genet. 2022 Jun 3;13:904536. doi: 10.3389/fgene.2022.904536. eCollection 2022.
Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures. GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC. We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen. We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies.
在肌肉浸润性膀胱癌（MIBC）的治疗过程中，耐药性和复发常常出现。MIBC中癌症干细胞（CSCs）的存在使得制定有效的治疗策略极具挑战性。我们旨在使用单细胞RNA测序方法来鉴定CSCs，评估其分子特征，并发现可能的治疗措施。利用GEO数据集GSE130001和GSE146137构建表达矩阵。在按类型鉴定细胞后，提取InferCNV推断出的恶性上皮细胞进行干性评估。对干性最高的细胞亚群进行加权基因共表达网络分析（WGCNA）和拟时间分析以鉴定关键基因。此外，我们在CTD中预测关键基因的药物敏感性关系，并通过siGDC预测药物与生存之间的相关性。我们发现在MIBC样本中存在一些CSCs。CSC群体在肿瘤发展过程中是异质性的，可分为静止型和增殖型CSCs。我们将DBI鉴定为静止型CSCs中的关键基因。对TCGA数据集的分析表明，较高的DBI表达表明较高的组织学分级。此外，我们预测对乙酰氨基酚可以降低DBI表达，从而降低CSCs的干性。因此，我们确定了对乙酰氨基酚的一种潜在新用途。我们系统地探索了肿瘤中的CSCs，并确定DBI可能是静止型CSCs中的关键基因和潜在治疗靶点。此外，我们证实对乙酰氨基酚可能是一种靶向CSCs的候选药物，增进了我们对靶向CSCs治疗策略的理解。
