Elucidating the Correlation between Leupaxin as a Prognostic Biomarker and Immunotherapeutic Efficacy in Esophageal Squamous Cell Carcinoma

Abstract

Abstract Background: Oesophageal cancer is a prevalent malignant tumour globally, yet it often receives subpar treatment. Recent interest in immunotherapy has instilled hope for cancer patients. However, further research is necessary to comprehend the mechanisms and roles of effective biomarker in oesophageal squamous carcinoma (ESCC). Methods: We investigated the expression, pathological and prognostic significance, protein interactions, pathway enrichment, immune microenvironment, correlations between immune regulators and infiltration of immune cells, associations with drug resistance genes, as well as chemosensitivity of leupaxin (LPXN) in ESCC. The relative expression of LPXN mRNA and protein was evaluated in both healthy surrounding tissues and ESCC tissues using quantitative polymerase chain reaction and immunohistochemistry, utilizing samples obtained from clinical cases. Furthermore, we investigated the potential role of LPXN in ESCC through a variety of techniques including cell proliferation assays, apoptosis assays, clonogenic assays, migration assays with or without extracellular matrix support. The co-expression of LPXN and PD-L1 at the protein level in oesophageal squamous cell lines was determined by western blotting. We validated the expression of the LPXN gene in ESCC using clinical samples and investigated the correlation between LPXN gene expression and the efficacy of immune therapy for ESCC. Results:Bioinformatic analysis revealed a favourable association between LPXN and prognosis in ESCC. LPXN and PD-L1 were found to be co-expressed, with LPXN strongly associated with the immune system, related pathways, microenvironment, regulators, cell infiltration levels, genes related to drug resistance, and chemosensitivity. The expression of LPXN in ESCC at both mRNA and protein levels was confirmed in clinical samples of cancerous and normal tissues. Cell-based experiments demonstrated that knockdown of LPXN resulted in decreased cell viability, invasion, proliferation, and migration in ESCC cell lines. In samples that responded well to therapy, LPXN and PD-L1 were overexpressed at the mRNA and protein levels. Conclusion: The results of our study have revealed the significance and involvement of the immune-related biomarker LPXN in the proliferation and migration processes of ESCC, thereby establishing a novel framework for the treatment of this disease.