关键词:

鳞状细胞癌, 喉部, 3-磷酸甘油醛脱氢酶, 预后, 免疫组化

Abstract:

Objective　To analyze the expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in laryngeal squamous cell carcinoma (LSCC) and its relationship with prognosis. Methods　The clinical information and RNA-seq expression profiles of tumor tissue samples from the patients with LSCC were analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The expression levels of GAPDH in cancerous tissue and adjacent normal tissue were compared. A retrospective analysis was conducted on 79 patients with LSCC diagnosed and surgically treated at Huangshi Central Hospital from January 2014 to June 2020. There were 67 males and 12 females who were 39 to 81 years old. The immunohistochemistry (IHC) was employed to detect the expression of GAPDH in these 79 patients, serving as external validation. The role of GAPDH in LSCC prognosis was evaluated using the Kaplan-Meier survival curves and univariate and multivariate Cox proportional hazards regression models. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) gene set enrichment analyses were conducted to reveal the tumor biological processes associated with GAPDH. The single-sample gene set enrichment analysis algorithm was used to analyze the relationship between GAPDH expression, immune function, and immune cell infiltration. χ² test was used for the statistical analysis. Results　The GAPDH expression level in the LSCC tissue was higher than that in the adjacent normal tissue (P<0.05), showing significant differences across lymph node stages, histological grades, and clinical stages (all P<0.05). The receiver operating characteristic curve indicated that GAPDH expression effectively distinguished LSCC from adjacent normal tissues (area under the curve=0.816). The patients with high GAPDH expression had lower overall survival and progression-free survival than those with low GAPDH expression (both P<0.05). The multivariate Cox analysis demonstrated that high GAPDH expression (HR=4.294, P<0.05) and positive IHC staining (HR=1.403, P<0.05) were independent risk factors for OS in patients with LSCC. The GO and KEGG enrichment analyses indicated that GAPDH might promote tumor progression participating in hypoxia regulation processes. GAPDH mRNA expression was negatively correlated with CC chemokine receptor, human leukocyte antigen function, and the infiltration levels of various immune cells (such as active B cells, active CD8⁺ T cells, dendritic cells, and central granulocytes) in tumors (all P<0.05). Conclusions　GAPDH is significantly overexpressed in LSCC tissue and has good diagnostic efficacy for distinguishing normal and cancerous tissues. As an independent prognostic factor for LSCC, GAPDH may contribute to the disease's development and progression through hypoxia and tumor immune microenvironment regulation, making it a potential target for LSCC diagnosis and therapy.

Key words:

Laryngeal squamous cell carcinoma, Glyceraldehyde-3-phosphate dehydrogenase, Prognosis, Immunohistochemistry