Li Xiunan, Guan Hewen, Ma Chuanyu, Dai Yunfei, Su Ji, Chen Xu, Yuan Qihang, Wang Jianbo
Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Department of Dermatology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
Aging (Albany NY). 2024 Jan 12;16(2):1414-1439. doi: 10.18632/aging.205436.
The MAPK signaling pathway significantly impacts cancer progression and resistance; however, its functions remain incompletely assessed across various cancers, particularly in kidney renal clear cell carcinoma (KIRC). Therefore, there is an urgent need for comprehensive pan-cancer investigations of MAPK signaling, particularly within the context of KIRC. In this research, we obtained TCGA pan-cancer multi-omics data and conducted a comprehensive analysis of the genomic and transcriptomic characteristics of the MAPK signaling pathway. For in-depth investigation in KIRC, status of MAPK pathway was quantitatively estimated by ssGSEA and Ward algorithm was utilized for cluster analysis. Molecular characteristics and clinical prognoses of KIRC patients with distinct MAPK activities were comprehensively explored using a series of bioinformatics algorithms. Subsequently, a combination of LASSO and COX regression analyses were utilized sequentially to construct a MAPK-related signature to help identify the risk level of each sample. Patients in the C1 subtype exhibited relatively higher levels of MAPK signaling activity, which were associated with abundant immune cell infiltration and favorable clinical outcomes. Single-cell RNA sequencing (scRNA-seq) analysis of KIRC samples identified seven distinct cell types, and endothelial cells in tumor tissues had obviously higher MAPK scores than normal tissues. The immunohistochemistry results indicated the reduced expression levels of PAPSS1, MAP3K11, and SPRED1 in KIRC samples. In conclusion, our study represents the first integration of bulk RNA sequencing and single-cell RNA sequencing to elucidate the molecular characteristics of MAPK signaling in KIRC, providing a solid foundation for precision oncology.
丝裂原活化蛋白激酶（MAPK）信号通路对癌症进展和耐药性有显著影响；然而，其在各种癌症中的功能仍未得到全面评估，尤其是在肾透明细胞癌（KIRC）中。因此，迫切需要对MAPK信号进行全面的泛癌研究，特别是在KIRC的背景下。在本研究中，我们获得了TCGA泛癌多组学数据，并对MAPK信号通路的基因组和转录组特征进行了全面分析。为了在KIRC中进行深入研究，通过单样本基因集富集分析（ssGSEA）定量估计MAPK通路状态，并利用沃德算法进行聚类分析。使用一系列生物信息学算法全面探索了具有不同MAPK活性的KIRC患者的分子特征和临床预后。随后，依次利用套索（LASSO）和COX回归分析构建了一个与MAPK相关的特征，以帮助识别每个样本的风险水平。C1亚型患者表现出相对较高水平的MAPK信号活性，这与丰富的免疫细胞浸润和良好的临床结果相关。对KIRC样本的单细胞RNA测序（scRNA-seq）分析确定了七种不同的细胞类型，肿瘤组织中的内皮细胞MAPK评分明显高于正常组织。免疫组织化学结果表明，KIRC样本中PAPSS1、MAP3K11和SPRED1的表达水平降低。总之，我们的研究首次整合了批量RNA测序和单细胞RNA测序，以阐明KIRC中MAPK信号的分子特征，为精准肿瘤学提供了坚实的基础。
