[Analysis of the correlation between the expression of WFDC2 in B cells of lung adenocarcinoma tissue and the survival rate of patients].

Objective To investigate the expression and clinical significance of whey acidic protein (WAP) 4-disulfide core domain 2/human epididymis protein 4 (WFDC2/HE4) in lung adenocarcinoma. Methods The expression of WFDC2 in normal lung tissues and lung adenocarcinoma tissues, the correlation between WFDC2 and the prognosis survival in patients with lung adenocarcinoma were analyzed using the BioGPS database, GEPIA database, Oncomine database and Kaplan-Meier Plotter databases. The expression of WFDC2 in cancer tissue T cells and B cells was analyzed using the Cancer Cell Line Encyclopedia (CCLE). The WFDC2-related genes and functional annotations of their gene ontology (GO), the pathway enrichment of Kyoto Gene and Genomic Encyclopedia (KEGG) were analyzed using the STRING database. The co-expression relationship, correlation and significance of WFDC2-related genes in lung adenocarcinoma were analyzed using the cBioPortal database. The expression of WFDC2 in immune infiltrates and its implication to survival prognosis in the patients with lung adenocarcinoma were analyzed using the Tumor Immune Estimation Resource (TIMER) database. Results BioGPS database analysis showed that the expression of WFDC2 was low in normal lung tissues, but none in T cells and B cells of normal human tissues. GEPIA database analysis showed that the expression of WFDC2 was higher in lung adenocarcinoma compared with normal lung tissues. Four hundred and fourteen samples of differential expression of WFDC2 were obtained from Oncomine database. Nineteen of them had increased WFDC2 expression with four in lung adenocarcinoma; fifteen of them had decreased WFDC2 expression with one in lung adenocarcinoma. Meta-analysis of 4 studies meeting the setting conditions showed that the expression level of WFDC2 was high in lung adenocarcinoma tissues. Kaplan-Meier Plotter database results showed that the overall survival (OS) time of patients with lung adenocarcinoma in the high WFDC2 expression group was significantly longer than that in the low WFDC2 expression group. CCLE analysis showed that the expression of WFDC2 in cancer tissue T cells and B cells was significantly higher than that in normal tissues. String database analysis showed that there were 30 genes associated with WFDC2, which were involved in 4 signaling pathways. The classification results from GO annotation indicated the enrichment in 4 cell components, 8 molecular functions, and 27 biological processes. The cBioPortal database showed that the correlation and difference between secretory leukocyte protease inhibitor (SLPI) and WFDC2 in lung adenocarcinoma were markedly significant (Pearson=0.26; Spearman=0.46; P=6.20E-28). TIMER database analysis showed that B cells with high expression of WFDC2 in the immune microenvironment significantly prolonged the survival prognosis of patients with lung adenocarcinoma for 1 year, 3 years, 5 years and 10 years. Conclusion WFDC2 is highly expressed in lung adenocarcinoma tissues with the anti-tumor immunosuppressive effect, which can significantly prolong OS of lung adenocarcinoma patients and be used as a candidate marker for investigating clinical prognosis of lung adenocarcinoma.