Overexpression of STOML1 is associated with good prognosis in nasopharyngeal carcinoma

Abstract

Nasopharyngeal carcinoma (NPC) is a prevalent head and neck malignancy characterized by high recurrence rate, adversely affecting patient prognosis. The present study aimed to identify key genes and mechanisms affecting NPC prognosis using DNA microarray, bioinformatics analysis and clinical data integration. The gene expression profile of patients with NPC with favorable (n=12) and unfavorable (n=8) prognoses was assessed using cDNA profiling. Bioinformatics analysis was performed to identify key prognostic factors, whilst immunohistochemistry assays were performed to evaluate the association between gene-protein expression in 107 NPC samples. The prognostic significance was assessed using Cox regression analysis, Kaplan-Meier curves, log-rank tests and receiver operating characteristic (ROC) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to assess the underlying mechanisms. cDNA profiling identified six genes, including stomatin like 1 (STOML1), as significant prognostic factors. The Kaplan-Meier Plotter and The Cancer Genome Atlas database indicated that the mRNA expression levels of STOML1 were significantly associated (P<0.05) with head and neck squamous cell carcinoma prognosis. In addition, tissue microarray analysis revealed that high protein expression levels of STOML1 were significantly associated (P<0.05) with improved overall survival (OS) and disease-free survival (DFS). Furthermore, univariate and multivariate Cox analyses demonstrated that STOML1 expression is an independent prognostic factor for OS and DFS. ROC analysis also revealed improved predictive accuracy for 5-year OS when combining STOML1 expression with tumor-node-metastasis (TNM) staging [area under the curve (AUC)=0.874; P<0.001], compared with TNM staging alone (AUC=0.715; P=0.043) and STOML1 expression alone (AUC=0.774; P=0.010). Finally, GO and KEGG analyses demonstrated that the identified genes were mainly involved in pathways associated with apoptosis and cancer progression. Overall, the results of the present study suggested that STOML1 could serve a crucial role in NPC progression and could therefore serve as a valuable biomarker for NPC diagnosis and prognosis.

Keywords: DNA microarray; nasopharyngeal carcinoma; prognosis; stomatin like 1.

Figure 1.

Differential gene expression analysis in patients with nasopharyngeal carcinoma with varying prognoses. (A) Volcano plot. (B) Heatmap. FDR, false discovery rate; STOML1, stomatin like 1; EGFR, epidermal growth factor receptor; RAB25, Ras-related protein 25; BASP1, brain acid soluble protein 1; RINT1, RAD50-interacting protein 1; U2SURP, U2 snRNP associated SURP domain containing.

Figure 2.

Differential mRNA expression of differentially expressed genes between HNSC and normal tissues, based on The Cancer Genome Atlas database analysis. (A) BASP1; (B) STOML1; (C) RINT1; (D) RAB25; and (E) U2SURP. HNSC, head and neck squamous cell carcinoma; BASP1, brain acid soluble protein 1; STOML1, stomatin like 1; RINT1, RAD50-interacting protein 1; RAB25, Ras-related protein 25; U2SURP, U2 snRNP associated SURP domain containing; T, tumor tissue; N, normal tissue.

Figure 3.

Association between mRNA expression levels of differentially expressed genes and overall survival in patients with head and neck squamous cell carcinoma, based on the Kaplan-Meier plotter database analysis. (A) BASP1; (B) STOML1; (C) RINT1; (D) RAB25; and (E) U2SURP. BASP1, brain acid soluble protein 1; STOML1, stomatin like 1; RINT1, RAD50-interacting protein 1; RAB25, Ras-related protein 25; U2SURP, U2 snRNP associated SURP domain containing; HR, hazard ratio.

Figure 4.

Association between BASP1 and STOML1 mRNA expression levels with OS and DFS in patients with nasopharyngeal carcinoma. (A) BASP1 and OS; (B) BASP1 and DFS; (C) STOML1 and OS; and (D) STOML1 and DFS. BASP1, brain acid soluble protein 1; STOML1, stomatin like 1; RINT1, RAD50-interacting protein 1; OS, overall survival; DFS, disease-free survival; HR, hazard ratio; CI, confidence interval.

Figure 5.

Time-dependent receiver operating characteristic curves of STOML1 protein expression, TNM staging system and their combination for evaluating the specificity and sensitivity in predicting 5-year overall survival in 107 patients with nasopharyngeal carcinoma. STOML1, stomatin like 1; TNM, tumor-node-metastasis; AUC, area under the curve.

Figure 6.

Analysis of the enriched pathways and functional characterization. (A) Pathway enrichment and (B) Gene Ontology functional analysis of differentially expressed genes associated with NPC prognosis in 20 patients with NPC. FDR, false discovery rate. NPC, nasopharyngeal carcinoma.

Figure 7.

Correlation analysis of mRNA expression between STOML1 and key apoptosis-related genes in head and neck squamous cell carcinoma, based on the Tumor Immune Estimation Resource 2.0 database. (A) BAX; (B) FAS; and (C) CASP9. STOML1, stomatin like 1; CASP9, caspase-9; TPM, transcripts per million.