Abstract
BackgroundThe SEC61 translocon gamma subunit (SEC61G) is a component of the SEC61 complex, which import protein into the endoplasmic reticulum. However, the correlation between SEC61G and disease prognosis in head and neck squamous cell carcinoma (HNSCC) remains unclear.MethodsSEC61G expression was analyzed using publicly available datasets. The association between SEC61G and disease prognosis was evaluated. SEC61G methylation and copy number variation were investigated and gene set enrichment analysis and gene ontology analyses identified SEC61G‐associated functions. We also investigated the correlation between SEC61G and immune cell infiltration. Finally, immunohistochemistry was used to detect SEC61G expression in oropharyngeal carcinoma.ResultsSEC61G was overexpressed in pan‐cancers, including HNSCC, and negatively correlated with overall survival (OS) (p < 0.001 for TCGA‐HNSCC and p = 0.019 for GSE65858). Moreover, SEC61G was an independent prognostic factor for OS in TCGA and GSE65858 [hazard ratio (HR) = 1.80, 95% CI: 1.35–2.39, p < 0.001; HR = 1.87, 95% CI: 1.14–3.07, p = 0.013, respectively). SEC61G DNA amplification (9.66% of patients) was significantly associated with poor OS (p = 0.034). SEC61G overexpression and DNA amplification negatively correlated with B cell (p < 0.001), CD8+ T cell (p < 0.001), CD4+ T cell (p < 0.001), macrophage (p < 0.05), neutrophil (p < 0.001), and dendritic cell infiltration (p < 0.001). Among patients with metastatic urothelial cancer received atezolizumab, patients with high SEC61G expression had an inferior OS (p = 0.006). Furthermore, SEC61G protein expression was also an independent prognostic factor of OS (HR = 2.46, 95% CI: 1.15–5.28, p = 0.021) and progression‐free survival (HR = 2.82, 95% CI: 1.36–5.85, p = 0.005) for oropharyngeal cancer.ConclusionsSEC61G is overexpressed in HNSCC and is an independent prognostic factor for OS. SEC61G DNA amplification contributes to overexpression and poor outcome. Interestingly, SEC61G correlates with immune cell infiltration in HNSCC. These findings suggest that SEC61G is a potential broad‐spectrum biomarker for prognosis in HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that accounts for 500,000 new cases every year globally[1, 2]
Sec61 translocon gamma subunit (SEC61G) is overexpressed in head and neck squamous cell carcinoma
The the Cancer Genome Atlas (TCGA) dataset analysis showed that regardless of the human papillomavirus (HPV) infection status, the expression of SEC61G was higher in head and neck squamous cell carcinoma (HNSCC) than in normal tissues
Summary
Head and neck squamous cell carcinoma (HNSCC) is a common malignancy that accounts for 500,000 new cases every year globally[1, 2]. Tumor-node-metastasis (TNM) classification, which considers the tumor size, location, and metastatic state, is used to develop treatment strategies and evaluate HNSCC prognosis[7] This system is not sufficient to direct all clinical treatments and predict every prognosis, because patients with the same TNM stage and treatment may have different clinical outcomes[8]. Some HNSCC tumors, such as human papillomavirus (HPV) associated oropharyngeal cancer, which are closely related to HPV inflection, can have a significantly better prognosis[9, 11]. Because of this heterogeneity, identifying stable broad-spectrum biomarkers is difficult. The correlation between SEC61G and disease prognosis in head and neck squamous cell carcinoma (HNSCC) remains unclear
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