HERPUD1 as a potential prognostic biomarker in lung cancer and association with migration and invasion

Abstract

Abstract Lung adenocarcinoma (LUAD) is the most prevalent type of lung cancer with unfavorable prognosis. Endoplasmic reticulum (ER) stress and the tumor immune microenvironment (TME) contribute to cancer progression. However, the role of ER stress and TME in LUAD remains poorly understood. Utilizing bioinformatics analysis, we identified HERPUD1 as a promising candidate gene among ER stress-related genes. HERPUD1 was found down-regulated in lung cancer tissues compared to normal tissues, with low expression HERPUD1 serving as a poor prognostic indicator. Immunofluorescence analysis indicated the subcellular localization of HERPUD1 within the cytoplasm, ER and plasma membrane. Cell functional experiments indicated that HERPUD1 overexpression significantly inhibited lung cancer cells proliferation and epithelial mesenchymal transformation (EMT). To further investigate the underlying mechanisms of HERPUD1 in LUAD, we performed GO and KEGG enrichment analyses. These analyses unveiled that upregulated HERPUD1 inhibited the JAK2/STAT3 pathway. Furthermore, immune infiltration analyses showed that a positive correlation between HERPUD1 and B cells, CD8 T cells and NK cells. Chemokine analysis showed that HERPUD1 may recruit DCs, T cells and monocytes/macrophages, and reduce the polarization of macrophages and neutrophils. Notably, high HERPUD1 expression indicated favorable chemotherapy and immunotherapy response after immune checkpoint blockade treatment. Collectively, our findings shed light on the critical role of ER stress in the context of LUAD, emphasizing the significance of HERPUD1 as a prospective therapeutic target and prognostic biomarker in LUAD.