Background and objective Lung squamous cell carcinoma(LUSC)is a subtypes of non-small cell lung cancer(NSCLC).It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway.Protocadherin-gamma subfamily B4(PCDHGB4)as a family member in LUSC was rarely reported.The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC us-ing bioinformatics methods.Methods The Cancer Genome Atlas(TCGA),cBioPortal and UALCAN databases were used to analyze the expression,prognosis,clinicopathological features,immune cell infiltration,immune regulatory genes,immune checkpoint inhibitors(ICIs),and methyltransferases of PCDHGB4 in LUSC.At the single cell level,we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations.In addition,we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis.Finally,enrichment analysis was performed based on the differentially expressed genes.Results Bioinformat-ics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues.Sur-vival analysis showed that increased PCDHGB4 expression was associated with poor prognosis.Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells,monocytes or macrophages,and dendritic cells.It was further found that PCD-HGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints,immune regulatory genes,and methyltransferases.Besides,enrichment analysis revealed that PCDHGB4 was involved in mul-tiple cancer-related pathways.Conclusion The expression of PCDHGB4 was low in LUSC.PCDHGB4 was related to the poor prognosis of patients,and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells.PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC.

BACKGROUND: Lung cancer is the most common malignant tumor in China, lung adenocarcinoma (LUAD) is the main type of lung cancer, which is a serious threat to people's life and health. At present, there are fewer studies on the role of Dikkopf1 (DKK1) in lung adenocarcinoma. The aim of this study was to investigate the role and potential prognostic value of DKK1 in the development of lung adenocarcinoma by bioinformatics methods. METHODS: Several databases, such as genotype-tissue expression (GTEx), The Cancer Genome Atlas (TCGA) and tumor-immune system interactions database (TISIDB), were used to analyze the expression, clinicopathological features, immune cell infiltration, prognosis and methylation of DKK1 in lung adenocarcinoma. Then, linked immune cell infiltration Omics database was used to analyze the co-expressed genes of DKK1 and their functional enrichment. Finally, 59 pathological samples of paraffin-embedded lung adenocarcinoma patients who underwent surgery at the Affiliated Cancer Hospital of Xinjiang Medical University between 2016 and 2017 were collected for the validation of the prognostic value of expression by immunohistochemistry (IHC) test. RESULTS: The results of bioconfidence analysis showed that the expression level of DKK1 in lung adenocarcinoma tissues was higher than that in normal tissues, the expression in advanced cancers was higher than that in early stages, and the experimental validation revealed that among 59 cases of lung adenocarcinoma, there were 15 cases of negative expression (25.4%), 18 cases of weakly positive expression (30.5%), and 26 cases of strongly positive expression (44.1%). The different expression of DKK1 is related to methylation, prognosis and the activities of various immune cells. Functional enrichment shows that DKK1 may be involved in skin development and cell-substrate junction, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis shows that DKK1 is related to ABC transporters. Bioinformatics analysis and clinical case specimens showed that high DKK1 expression was associated with poorer prognosis in patients with lung adenocarcinoma. CONCLUSIONS High expression of DKK1 in lung adenocarcinoma is associated with poor prognosis. DKK1 is closely associated with tumor immune cell infiltration and pathways. DKK1 can be considered as a potential prognostic marker and a novel target for immunotherapy of lung adenocarcinoma.