Correlation between PTHLH gene expression and anti-tumor immunity in lung squamous cell carcinoma
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Abstract:
Objective: To analyze the association of parathyroid hormone-like hormone (PTHLH) with the prognosis as well as the immune cell infiltration in the tumor microenvironment (TME) of patients with lung squamous cell carcinoma (LSCC). Methods: The expression pattern of PTHLH in pan-cancer was analyzed by UALCAN, TIMER, and cBioPortal databases, and the Kaplan-Meier Plotter database was used to analyze the relationship between the expression of PTHLH in LSCC and the prognosis of patients. The cancer tissues and paracancerous tissues of 24 LSCC patients who underwent surgical resection in the Gansu Cancer Hospital from January 2017 to December 2020 were selected for this study. The mRNA and protein expression levels of PTHLH in LSCC tissues were verified by qPCR and WB, and the expression levels of various chemokines and MHC molecules were detected by qPCR. Then, the correlation between PTHLH expression and immune infiltration in the TME of LSCC was investigated by the TIMER database combined with CIBERSORT deconvolution method.Results: Compared with para-cancerous tissues, the mRNA and protein expression levels of PTHLH were significantly higher in LSCC tissues (both P<0.05). Furthermore, the OS of LSCC patients with high PTHLH expression was significantly shortened (P<0.01). In addition, the expression of PTHLH was closely related to the TME in patients with LSCC (P<0.01). The expression of PTHLH was negatively correlated with immune infiltrates, including B cells, CD8+ T cells, CD4+ T cells, neutrophils and dendritic cells (r=-0.142, -0.123, -0.224, -0.166,-0.213, all P<0.01). Overexpression of PTHLH inhibited the expression of chemokines and MHC molecules, thereby inhibiting inflammatory responses, immune infiltration, anti-tumor immune responses, etc. Additionally, the expression of PTHLH was negatively correlated with the levels of immune checkpoint molecules CTLA-4, PDCD1 and TIGIT (r=-0.340, -0.441, -0.38, all P<0.01). Conclusion: PTHLH is associated with tumor immunosuppression and is expected to serve as a potential biomarker for predicting immunotherapy effect and prognosis in patients with LSCC.