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肥胖和与脂质代谢相关的基因预测口腔鳞状细胞癌患者的生存状况不佳。

Obesity and genes related to lipid metabolism predict poor survival in oral squamous cell carcinoma.

机构信息

Department of Oral Medicine, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, China.

Department of Intensive Care Unit, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.

出版信息

Oral Oncol. 2019 Feb;89:14-22. doi: 10.1016/j.oraloncology.2018.12.006. Epub 2018 Dec 14.

Abstract

OBJECTIVES

Obesity is an important risk factor for several malignancies, but its effect on oral squamous cell carcinoma (OSCC) prognosis is controversial. We aimed to disclose the association between obesity and the OSCC outcome, and explore the potential of some lipid metabolism-related genes as biomarkers for prognostic prediction.

MATERIALS AND METHODS

A total of 576 patients diagnosed as T1/2N0M0 OSCC without prediagnosis weight loss was included in this retrospective study. These patients were grouped according to body mass index (BMI). The univariate and multivariate analysis were used to compare the progression-free survival (PFS) and disease specific survival (DSS) between groups. Propensity score matching (PSM) was adopted to minimize confounders. Data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were employed to analyze the potential of some lipid metabolism-related genes for OSCC prognosis prediction.

RESULTS

The PFS (P = 0.023) and DSS (P = 0.047) were poorer in obese patients than in normal weight ones. Obesity was an independent risk factor for PFS (Hazard Ratio = 2.016, 95% Confidence Interval 1.101-3.693, P = 0.023) and DSS (Hazard Ratio = 2.022, 95% Confidence Interval 1.040-3.932, P = 0.038). Furthermore, the PSM matched cohort analysis revealed that obesity was associated with poor prognosis of OSCC patients. Finally, 72 dysregulated lipid metabolism-related genes were identified in OSCC, and a combining signature of TGFB1, SPP1, and SERPINE1 was defined as a biomarker for prognostic prediction.

CONCLUSIONS

Obesity is an independent risk factor for T1/2N0M0 OSCC, and a combining signature of TGFB1, SPP1, and SERPINE1 may be applied to predict prognosis of OSCC patients.

摘要

目的

肥胖是多种恶性肿瘤的重要危险因素,但它对口腔鳞状细胞癌(OSCC)预后的影响仍存在争议。本研究旨在揭示肥胖与 OSCC 结局之间的关联,并探讨一些脂质代谢相关基因作为预后预测标志物的潜力。

材料和方法

本回顾性研究共纳入 576 例 T1/2N0M0 期 OSCC 患者,且无诊断前体重减轻。根据体重指数(BMI)将这些患者分为两组。采用单因素和多因素分析比较两组之间的无进展生存期(PFS)和疾病特异性生存期(DSS)。采用倾向评分匹配(PSM)以最小化混杂因素。从基因表达综合数据库(GEO)和癌症基因组图谱(TCGA)中获取数据,以分析一些脂质代谢相关基因对 OSCC 预后预测的潜力。

结果

肥胖患者的 PFS(P=0.023)和 DSS(P=0.047)均较差。肥胖是 PFS(风险比[HR]=2.016,95%置信区间 1.101-3.693,P=0.023)和 DSS(HR=2.022,95%置信区间 1.040-3.932,P=0.038)的独立危险因素。此外,PSM 匹配队列分析显示肥胖与 OSCC 患者的不良预后相关。最后,在 OSCC 中鉴定出 72 个失调的脂质代谢相关基因,并定义 TGFB1、SPP1 和 SERPINE1 的组合特征作为预后预测的标志物。

结论

肥胖是 T1/2N0M0 OSCC 的独立危险因素,TGFB1、SPP1 和 SERPINE1 的组合特征可能用于预测 OSCC 患者的预后。

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