Work

PAK6 drives tumor microenvironment remodeling in nasopharyngeal carcinoma with lymph node necrosis: implications for distant metastasis and survival

Year: 2025

Type: article

Abstract: BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignancy commonly characterized by lymph node metastasis, with lymph node necrosis (LNN) often associated with poor clinical outcomes. This study aims to elucidate the impact of LNN on survival outcomes in NPC patients and explore the underlying molecular mechanisms. METHODS: We performed RNA sequencing on 147 NPC samples from Fujian Cancer Hospital to identify differentially expressed genes (DEGs) between LNN and non-LNN samples. DEGs were selected using univariate logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression to identify genes associated with metastasis, and a prognostic risk model was constructed. p21-activated kinase 6 (PAK6) was identified as a key gene, followed by functional pathway analysis and investigation of immune infiltration. The mRNA expression level of PAK6 was validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR), and protein expression in clinical tissues was evaluated using immunohistochemistry (IHC). Functional assays including colony formation, CCK-8, and wound healing assays were performed to assess the impact of PAK6 on cell proliferation, migration, and clonogenic ability. RESULTS: RNA sequencing analysis identified 258 DEGs between LNN and non-LNN samples. Univariate logistic regression and LASSO regression revealed 11 metastasis-associated genes, which were used to construct a prognostic risk model. PAK6 was identified as a key gene, with high expression correlating with poor prognosis (p < 0.05). Functional analysis indicated PAK6's involvement in the PI3K-Akt signaling pathway, and immune infiltration analysis suggested its association with CD8+ T cells. RT-qPCR confirmed elevated PAK6 mRNA expression in tumor tissues, and immunohistochemistry showed higher PAK6 protein levels in primary tumors, metastatic lesions, and necrotic regions. Functional assays demonstrated that PAK6 knockdown inhibited NPC cell proliferation, colony formation, and migration. CONCLUSION: These findings highlight LNN as a critical prognostic factor in NPC and suggest that PAK6 could be a promising therapeutic target for improving treatment outcomes in NPC patients.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115662