Abstract
BACKGROUND: Lung adenocarcinoma (LUAD) is a highly prevalent and deadly form of lung cancer and is a significant health concern worldwide. Although the expression of serine protease 3 (PRSS3) is elevated in certain cancers, its function in LUAD is yet unclear. The aim of this study was to investigate the mechanism of PRSS3 in lung adenocarcinoma, and validate PRSS3 as a reliable prognostic biomarker in lung adenocarcinoma. METHODS: The Cancer Genome Atlas (TCGA) provides RNA expression data and patient medical information for LUAD patients. To determine which genes are expressed differently in LUAD and normal lung tissues, we carefully examined these data. We then used Cox regression analysis to examine the expression and survival data to pinpoint the genes that are strongly associated with patient survival. The PRSS3 gene affects patient prognosis. Afterward, we divided LUAD patients into low- and high-expression groups on the basis of the median PRSS3 expression to examine the relationship between immune cells and PRSS3. The results of the CIBERSORT and CIBERSORTx studies revealed correlations between PRSS3 and the degree of infiltration of several immune cell types. After the groups with low and high PRSS3 expressions were compared, PRSS3-related genes were identified, and functional enrichment analysis was performed. Furthermore, a model was developed to predict patient prognosis according to clinical characteristics and PRSS3 expression. After the bioinformatics analyses were completed, we validated the differential expression of PRSS3 in samples obtained from our center via Western blotting and immunohistochemistry (IHC). RESULTS: We found that PRSS3 expression is highly upregulated in LUAD and that high PRSS3 expression is associated with a poorer prognosis in the TCGA database. Single-sample gene enrichment analysis revealed a strong correlation between PRSS3 and the immunological microenvironment. The clinical model developed on the basis of the PRSS3 showed great accuracy and can be used as a significant diagnostic indicator for LUAD. Western blotting and IHC confirmed a substantial increase in PRSS3 expression in LUAD. Herein, we analyzed an available dataset for a clinical cohort and revealed that elevated levels of PRSS3 are indicative of unfavorable outcomes in patients diagnosed with LUAD. CONCLUSIONS: PRSS3 is significantly upregulated in LUAD and can be used as a marker for LUAD diagnosis and prognosis assessment. Further study of PRSS3 could provide valuable insight into the mechanisms underlying the occurrence and progression of LUAD.