Proteomics analysis and immune profiling reveal regulators of PD-L1 in oesophageal squamous cell carcinoma.

BACKGROUND: Proteomics studies have advanced our comprehension of cancer biology, accelerated targeted therapy, and improved patient outcomes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.