Zhou Limin, Liu Jiejie, Yao Peipei, Liu Xing, Chen Fei, Chen Yu, Zhou Li, Shen Chao, Zhou You, Du Xin, Hu Junbo
Tongji Medical College, Maternal and Child Health Hospital of Hubei Province, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430070, China.
State Key Laboratory of Virology, College of Life Sciences and Frontier Science Center for Immunology and Metabolism, RNA Institute, Wuhan University, Wuhan, 430072, China.
J Transl Med. 2024 Dec 31;22(1):1163. doi: 10.1186/s12967-024-06011-y.
As a prevalent and deadly malignant tumor, the treatment outcomes for late-stage patients with cervical squamous cell carcinoma (CSCC) are often suboptimal. Previous studies have shown that tumor progression is closely related with tumor metabolism and microenvironment reshaping, with disruptions in energy metabolism playing a critical role in this process. To delve deeper into the understanding of CSCC development, our research focused on analyzing the tumor microenvironment and metabolic characteristics across different regions of tumor tissue.
Utilizing spatial transcriptomics (ST) sequencing technology, we conducted a study on FFPE (formalin-fixed paraffin-embedded) tumor samples from CSCC patients. Coupled with single-cell RNA sequencing (scRNA-seq) data after deconvolution, we described spatial distribution maps of tumor leading edge and core regions in detail. Tumor tissues were classified into hypermetabolic and hypometabolic regions to analyze the metabolism profiles and tumor differentiation degree across different spatial areas. We also employed The Cancer Genome Atlas (TCGA) database to examine the analysis results of ST data.
Our findings indicated a more complex tumor microenvironment in hypermetabolic regions. Cell-cell communication analysis showed that various cells in tumor microenvironment were influenced by the signalling molecule APP released by cancer cells and higher expression of APP was observed in hypermetabolic regions. Furthermore, our results revealed the correlation between APP and the transcription factor TRPS1. Both APP and TRPS1 demonstrated significant effects on cancer cell proliferation, migration, and invasion, potentially contributing to tumor progression.
Utilizing ST, scRNA-seq, and TCGA database, we examined the spatial metabolic profiles of CSCC tissues, including metabolism distribution, metabolic variations, and the relationship between metabolism and tumor differentiation degree. Additionally, potential cancer-promoting factors were proposed, offering a valuable foundation for the development of more effective treatment strategies for CSCC.
作为一种常见且致命的恶性肿瘤，晚期宫颈鳞状细胞癌（CSCC）患者的治疗效果往往不尽人意。先前的研究表明，肿瘤进展与肿瘤代谢和微环境重塑密切相关，能量代谢紊乱在这一过程中起关键作用。为了更深入地了解CSCC的发展，我们的研究聚焦于分析肿瘤组织不同区域的肿瘤微环境和代谢特征。
利用空间转录组学（ST）测序技术，我们对CSCC患者的福尔马林固定石蜡包埋（FFPE）肿瘤样本进行了研究。结合去卷积后的单细胞RNA测序（scRNA-seq）数据，我们详细描述了肿瘤前沿和核心区域的空间分布图。将肿瘤组织分为高代谢和低代谢区域，以分析不同空间区域的代谢谱和肿瘤分化程度。我们还使用了癌症基因组图谱（TCGA）数据库来检验ST数据的分析结果。
我们的研究结果表明，高代谢区域的肿瘤微环境更为复杂。细胞间通讯分析表明，肿瘤微环境中的各种细胞受到癌细胞释放的信号分子APP的影响，并且在高代谢区域观察到APP的表达更高。此外，我们的结果揭示了APP与转录因子TRPS1之间的相关性。APP和TRPS1均对癌细胞的增殖、迁移和侵袭具有显著影响，可能促进肿瘤进展。
利用ST、scRNA-seq和TCGA数据库，我们研究了CSCC组织的空间代谢谱，包括代谢分布、代谢变化以及代谢与肿瘤分化程度之间的关系。此外，还提出了潜在的促癌因素，为开发更有效的CSCC治疗策略提供了有价值的基础。
