Li Yuying, Yuan Xiaoyi, Yin Xing-Feng, Zheng Dandan, Shi Fujin, Liu Danya, Hu Liling, Shi Xinyu, Wen Nengqiao, He Qing-Yu, Yang Hong, Zhang Chris Zhiyi
MOE Key Laboratory of Tumor Molecular Biology and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China.
Department of Pathology, State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
Br J Cancer. 2025 Jun 10. doi: 10.1038/s41416-025-03068-4.
Proteomics studies have advanced our comprehension of cancer biology, accelerated targeted therapy, and improved patient outcomes.
High-resolution mass spectrometry and immune profiling based on immunohistochemistry and multiple immunohistochemistry were employed to investigate proteomic and immune landscapes in oesophageal squamous cell carcinoma (ESCC) and explore the regulators of PD-L1 in ESCC. Molecular validation was performed using qRT-PCR, western blotting, and in vitro functional assays.
Proteomic profiling of 89 treatment-naive ESCC specimens identified over 9300 proteins, with 6900 proteins detected across most samples. Proteome-based stratification identified three subtypes related to diverse clinical and molecular features. Combined proteomics and immune analyses revealed core proteins associated with the immune landscape in ESCC. Further, integrated proteomics, transcriptomics, and immune profiling nominated COTL1 as a potential regulator of PD-L1 in ESCC. Overexpression of COTL1 upregulated both mRNA and protein levels of PD-L1 and promoted cell proliferation in ESCC. Patients with high COTL1 protein expression were likely to have a poor prognosis, along with increased infiltration of CD4+CD8+ and CD4+GrB+ cells.
Collectively, our integrative analysis enables a more comprehensive understanding of the proteomic and immune landscape of ESCC and implicates COTL1 as a potential modulator of PD-L1 and immune cell infiltration.
蛋白质组学研究增进了我们对癌症生物学的理解，加速了靶向治疗，并改善了患者预后。
采用高分辨率质谱以及基于免疫组织化学和多重免疫组织化学的免疫分析，以研究食管鳞状细胞癌（ESCC）的蛋白质组学和免疫格局，并探索ESCC中PD-L1的调节因子。使用qRT-PCR、蛋白质免疫印迹和体外功能分析进行分子验证。
对89例未经治疗的ESCC标本进行蛋白质组分析，鉴定出9300多种蛋白质，大多数样本中检测到6900种蛋白质。基于蛋白质组的分层确定了与不同临床和分子特征相关的三种亚型。蛋白质组学和免疫分析相结合，揭示了与ESCC免疫格局相关的核心蛋白质。此外，整合蛋白质组学、转录组学和免疫分析表明，COTL1是ESCC中PD-L1的潜在调节因子。COTL1的过表达上调了ESCC中PD-L1的mRNA和蛋白质水平，并促进了细胞增殖。COTL1蛋白高表达的患者预后可能较差，同时CD4+CD8+和CD4+GrB+细胞浸润增加。
总体而言，我们的综合分析能够更全面地了解ESCC的蛋白质组学和免疫格局，并表明COTL1是PD-L1和免疫细胞浸润的潜在调节因子。
