HPV 相关与吸烟相关头颈部癌症的血浆代谢表型与患者生存。
Plasma Metabolic Phenotypes of HPV-Associated versus Smoking-Associated Head and Neck Cancer and Patient Survival.
机构信息
Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, Georgia.
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University, Atlanta, Georgia.
出版信息
Cancer Epidemiol Biomarkers Prev. 2021 Oct;30(10):1858-1866. doi: 10.1158/1055-9965.EPI-21-0576. Epub 2021 Aug 10.
BACKGROUND
Metabolic differences between human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) and smoking-associated HNSCC may partially explain differences in prognosis. The former relies on mitochondrial oxidative phosphorylation (OXPHOS) while the latter relies on glycolysis. These differences have not been studied in blood.
METHODS
We extracted metabolites using untargeted liquid chromatography high-resolution mass spectrometry from pretreatment plasma in a cohort of 55 HPV-associated and 82 smoking-associated HNSCC subjects. Metabolic pathway enrichment analysis of differentially expressed metabolites produced pathway-based signatures. Significant pathways ( < 0.05) were reduced via principal component analysis and assessed with overall survival via Cox models. We classified each subject as glycolytic or OXPHOS phenotype and assessed it with survival.
RESULTS
Of 2,410 analyzed metabolites, 191 were differentially expressed. Relative to smoking-associated HNSCC, bile acid biosynthesis ( < 0.0001) and octadecatrienoic acid beta-oxidation ( = 0.01), were upregulated in HPV-associated HNSCC, while galactose metabolism ( = 0.001) and vitamin B6 metabolism ( = 0.01) were downregulated; the first two suggest an OXPHOS phenotype while the latter two suggest glycolytic. First principal components of bile acid biosynthesis [HR = 0.52 per SD; 95% confidence interval (CI), 0.38-0.72; < 0.001] and octadecatrienoic acid beta-oxidation (HR = 0.54 per SD; 95% CI, 0.38-0.78; < 0.001) were significantly associated with overall survival independent of HPV and smoking. The glycolytic versus OXPHOS phenotype was also independently associated with survival (HR = 3.17; 95% CI, 1.07-9.35; = 0.04).
CONCLUSIONS
Plasma metabolites related to glycolysis and mitochondrial OXPHOS may be biomarkers of HNSCC patient prognosis independent of HPV or smoking. Future investigations should determine whether they predict treatment efficacy.
IMPACT
Blood metabolomics may be a useful marker to aid HNSCC patient prognosis.
背景
人乳头瘤病毒（HPV）相关头颈部鳞状细胞癌（HNSCC）和吸烟相关 HNSCC 之间的代谢差异可能部分解释了预后的差异。前者依赖于线粒体氧化磷酸化（OXPHOS），而后者依赖于糖酵解。这些差异在血液中尚未得到研究。
方法
我们从 55 例 HPV 相关和 82 例吸烟相关 HNSCC 患者的预处理血浆中提取了非靶向液相色谱高分辨率质谱的代谢物。对差异表达代谢物进行代谢途径富集分析，产生基于途径的特征。通过主成分分析降低有意义的途径（<0.05），并通过 Cox 模型评估与总生存期的关系。我们将每个受试者分类为糖酵解或 OXPHOS 表型，并评估其与生存的关系。
结果
在分析的 2410 种代谢物中，有 191 种差异表达。与吸烟相关的 HNSCC 相比，HPV 相关的 HNSCC 中胆汁酸生物合成（<0.0001）和十八碳三烯酸β-氧化（=0.01）上调，而半乳糖代谢（=0.001）和维生素 B6 代谢（=0.01）下调；前两者提示 OXPHOS 表型，后两者提示糖酵解表型。胆汁酸生物合成的第一主成分[每标准差 HR=0.52；95%置信区间（CI）0.38-0.72；<0.001]和十八碳三烯酸β-氧化（HR=0.54 每标准差；95%CI，0.38-0.78；<0.001）与 HPV 和吸烟无关，与总生存期显著相关。糖酵解与 OXPHOS 表型也与生存独立相关（HR=3.17；95%CI，1.07-9.35；=0.04）。
结论
与糖酵解和线粒体 OXPHOS 相关的血浆代谢物可能是独立于 HPV 或吸烟的 HNSCC 患者预后的生物标志物。未来的研究应该确定它们是否可以预测治疗效果。
影响
血液代谢组学可能是一种有用的标志物，有助于 HNSCC 患者的预后。
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