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High expression of oxidative phosphorylation genes predicts improved survival in squamous cell carcinomas of the head and neck and lung.

ABSTRACT: Mitochondrial activity is a critical component of tumor metabolism, with profound implications for tumorigenesis and treatment response. We analyzed clinical, genomic and expression data from patients with oral cavity squamous cell carcinoma (OCSCC) in order to map metabologenomic events which may correlate with clinical outcomes and identified nuclear genes involved in oxidative phosphorylation and glycolysis (OXPHOG) as a critical predictor of patient survival. This correlation was validated in a secondary unrelated set of lung squamous cell carcinoma (LUSC) and was shown to be driven largely by over-expression of nuclear encoded components of the mitochondrial electron transport chain (ETC) coordinated with an increase in tumor mitochondrial DNA copy number and a strong threshold effect on patient survival. OCSCC and LUSC patients with a favorable OXPHOG signature demonstrated a dramatic (>2fold) improvement in survival compared to their counterparts. Differential OXPHOG expression correlated with varying tumor immune infiltrates suggesting that the interaction between tumor metabolic activity and tumor associated immunocytes may be a critical driver of improved clinical outcomes in this patient subset. These data provide strong support for studies aimed at mechanistically characterizing the interaction between tumor mitochondrial activity and the tumor immune microenvironment.

SUBMITTER: Frederick M

PROVIDER: S-EPMC7156383 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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High expression of oxidative phosphorylation genes predicts improved survival in squamous cell carcinomas of the head and neck and lung.

Frederick Mitchell M Skinner Heath D HD Kazi Sawad A SA Sikora Andrew G AG Sandulache Vlad C VC

Scientific reports 20200414 1

Mitochondrial activity is a critical component of tumor metabolism, with profound implications for tumorigenesis and treatment response. We analyzed clinical, genomic and expression data from patients with oral cavity squamous cell carcinoma (OCSCC) in order to map metabologenomic events which may correlate with clinical outcomes and identified nuclear genes involved in oxidative phosphorylation and glycolysis (OXPHOG) as a critical predictor of patient survival. This correlation was validated i ...[more]

PMID: 32286489

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Project description:Background: Overexpression of the membrane protein SEC61 translocon gamma subunit (SEC61G) has been observed in a variety of cancers; however, its role in head and neck squamous cell carcinomas (HNSCC) is unknown. This study aimed to elucidate the relationship between SEC61G and HNSCC based on data from The Cancer Genome Atlas (TCGA) database. Methods: Data for HNSCC patients were collected from TCGA and the expression level of SEC61G was compared between paired HNSCC and normal tissues using the Wilcoxon rank-sum test. The relationship between clinicopathologic features and SEC61G expression was also analyzed using the Wilcoxon rank-sum test and logistic regression. Receiver operating characteristic (ROC) curves were generated to evaluate the value of SEC61G as a binary classifier using the area under the curve (AUC value). The association of clinicopathologic characteristics with prognosis in HNSCC patients was assessed using Cox regression and the Kaplan-Meier methods. A nomogram, based on Cox multivariate analysis, was used to predict the impact of SEC61G on prognosis. Functional enrichment analysis was performed to determine the hallmark pathways associated with differentially expressed genes in HNSCC patients exhibiting high and low SEC61G expression. Results: The expression of SEC61G was significantly elevated in HNSCC tissues compared to normal tissues (P < 0.001). The high expression of SEC61G was significantly correlated with the T stage, M stage, clinical stage, TP53 mutation status, PIK3CA mutation status, primary therapy outcome, and cervical lymph node dissection (all P < 0.05). Meanwhile, ROC curves suggested the significant diagnostic ability of SEC61G for HNSCC (AUC = 0.923). Kaplan-Meier survival analysis showed that patients with HNSCC characterized by high SEC61G expression had a poorer prognosis than patients with low SEC61G expression (hazard ratio = 1.95, 95% confidence interval 1.48-2.56, P < 0.001). Univariate and multivariate analyses revealed that SEC61G was independently associated with overall survival (P = 0.027). Functional annotations indicated that SEC61G is involved in pathways related to translation and regulation of SLITs/ROBOs expression, SRP-dependent co-translational protein targeting to the membrane, nonsense-mediated decay, oxidative phosphorylation, and Parkinson's disease. Conclusion: SEC61G plays a vital role in HNSCC progression and prognosis; it may, therefore, serve as an effective biomarker for the prediction of patient survival.

Dataset Information

High expression of oxidative phosphorylation genes predicts improved survival in squamous cell carcinomas of the head and neck and lung.

Publications

High expression of oxidative phosphorylation genes predicts improved survival in squamous cell carcinomas of the head and neck and lung.

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