A multi-omics analysis reveals KDELR1 promotes malignant progression and correlates with tumor microenvironment in head and neck squamous cell carcinoma.

KDELR1, a constituent of the KDEL endoplasmic reticulum protein retention receptors family, is implicated in immune responses and cancers progression. In this study, we delineate the clinicopathological significance and oncogenic role of KDELR1 in head and neck squamous cell carcinoma (HNSCC) through a comprehensive multi-omics approach. KDELR1 expression is correlated with tumor grade, tumor stage, lymph node metastasis, clinical stage and poor prognosis in HNSCC. Moreover, our results indicate a marked upregulation of KDELR1 expression in primary tumor tissues compared to normal and dysplasia tissues. Furthermore, increased KDELR1 expression is associated with tumor progression and indicates an unfavorable prognosis in HNSCC. Functional enrichment analysis highlights the involvement of KDELR1 in HNSCC malignant progression. Depletion of KDELR1 inhibits proliferation, stemness, migration and invasion in HNSCC cells. Bioinformatics analysis results indicate that KDELR1 promotes HNSCC progression with regulating wnt signaling pathway and CTNNB1 expression. Of note, KDELR1 is associated with HNSCC tumor microenvironment compositions, especially positively correlating with cancer associated fibroblasts and negatively correlating with CD8+ T cells and B cells infiltration. Collectively, these findings indicate that KDELR1 as an oncogene in driving progression and correlates with tumor microenvironment, suggesting its potential as a promising biomarker and a therapeutic target in HNSCC.