Department of Pathology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Department of Thoracic Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241293485. doi: 10.1177/15330338241293485.
Esophageal Squamous Cell Carcinoma (ESCC) poses a significant health challenge in China due to its high incidence and mortality. Single-cell transcriptomics has transformed the approach to cancer research, allowing detailed analysis of cellular and molecular heterogeneity. The interaction between the transcription factor STAT1 and the tumor suppressor LHPP is crucial, potentially influencing cancer progression and therapeutic outcomes.
This study aims to explore the molecular mechanisms and cellular dynamics underlying ESCC, with a focus on the role of transcription factors, particularly STAT1, and its regulatory relationship with LHPP, in the pathogenesis of ESCC.
Utilizing single-cell transcriptomics data sourced from the public database GEO (GSE160269), we identified major cell types and their transcriptomic changes in ESCC patients. Differential gene expression profiles were examined to understand the dynamics of the tumor microenvironment (TME). A cohort of 21 ESCC patients was recruited to validate the findings. Furthermore, in ESCC cell lines, we validated the transcriptional regulatory relationship between STAT1 and LHPP.
Our analysis identified six major cell types within the ESCC microenvironment, revealing significant changes in cellular composition and gene expression profiles associated with tumorigenesis. Notably, a novel association between STAT1's regulatory role over LHPP was observed, suggesting a complex regulatory loop in ESCC pathogenesis. Elevated STAT1 and reduced LHPP expression were confirmed in patient samples with STAT1 negatively regulates LHPP expression at the promoter level; when the promoter binding motif regions were mutated, the transcriptional repression ability on LHPP was weakened.
The study highlights STAT1 as a core regulator in ESCC, directly influencing LHPP expression. The findings offer novel insights into the molecular mechanisms driving ESCC, shedding light on the cellular alterations and gene regulation dynamics within the ESCC microenvironment. This research provides a foundation for developing targeted therapeutic strategies, potentially utilizing the STAT1-LHPP axis as a focal point in ESCC treatment and prognosis.
食管鳞状细胞癌（ESCC）在中国发病率和死亡率高，对健康构成重大挑战。单细胞转录组学改变了癌症研究方法，使对细胞和分子异质性的详细分析成为可能。转录因子 STAT1 与肿瘤抑制因子 LHPP 之间的相互作用至关重要，可能影响癌症的进展和治疗效果。
本研究旨在探讨 ESCC 的分子机制和细胞动态，重点研究转录因子，特别是 STAT1，及其与 LHPP 的调控关系在 ESCC 发病机制中的作用。
利用公共数据库 GEO（GSE160269）中的单细胞转录组学数据，我们鉴定了 ESCC 患者中主要的细胞类型及其转录组变化。通过检查差异基因表达谱来了解肿瘤微环境（TME）的动态。招募了 21 名 ESCC 患者的队列来验证这些发现。此外，在 ESCC 细胞系中，我们验证了 STAT1 和 LHPP 之间的转录调控关系。
我们的分析确定了 ESCC 微环境中的六种主要细胞类型，揭示了与肿瘤发生相关的细胞组成和基因表达谱的显著变化。值得注意的是，我们观察到 STAT1 对 LHPP 的调节作用之间存在一个新的关联，表明在 ESCC 发病机制中存在一个复杂的调节环路。在患者样本中证实了 STAT1 的表达升高和 LHPP 的表达降低，STAT1 负调控 LHPP 在启动子水平的表达；当启动子结合基序区域发生突变时，对 LHPP 的转录抑制能力减弱。
该研究强调了 STAT1 作为 ESCC 的核心调节剂，直接影响 LHPP 的表达。研究结果提供了有关驱动 ESCC 的分子机制的新见解，揭示了 ESCC 微环境中的细胞变化和基因调控动态。这项研究为开发靶向治疗策略提供了基础，可能将 STAT1-LHPP 轴作为 ESCC 治疗和预后的重点。
