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肾细胞癌:利用 CT 特征预测 RUNX3 甲基化水平及其对生存的影响。

Renal cell carcinoma: predicting RUNX3 methylation level and its consequences on survival with CT features.

机构信息

Department of Radiation Oncology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, Guangdong Province, People's Republic of China.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine & The Second Clinical College of Guangzhou University of Chinese Medicine & Guangdong Provincial Hospital of Chinese Medicine, 111 Da De Lu, Guangzhou, 510120, Guangdong Province, People's Republic of China.

出版信息

Eur Radiol. 2019 Oct;29(10):5415-5422. doi: 10.1007/s00330-019-06049-3. Epub 2019 Mar 15.

DOI:10.1007/s00330-019-06049-3
PMID:30877466
Abstract

PURPOSE

To investigate associations between CT imaging features, RUNX3 methylation level, and survival in clear cell renal cell carcinoma (ccRCC).

MATERIALS AND METHODS

Patients were divided into high RUNX3 methylation and low RUNX3 methylation groups according to RUNX3 methylation levels (the threshold was identified by using X-tile). The CT scanning data from 106 ccRCC patients were retrospectively analyzed. The relationship between RUNX3 methylation level and overall survivals was evaluated using the Kaplan-Meyer analysis and Cox regression analysis (univariate and multivariate). The relationship between RUNX3 methylation level and CT features was evaluated using chi-square test and logistic regression analysis (univariate and multivariate).

RESULTS

β value cutoff of 0.53 to distinguish high methylation (N = 44) from low methylation tumors (N = 62). Patients with lower levels of methylation had longer median overall survival (49.3 vs. 28.4) months (low vs. high, adjusted hazard ratio [HR] 4.933, 95% CI 2.054-11.852, p < 0.001). On univariate logistic regression analysis, four risk factors (margin, side, long diameter, and intratumoral vascularity) were associated with RUNX3 methylation level (all p < 0.05). Multivariate logistic regression analysis found that three risk factors (side: left vs. right, odds ratio [OR] 2.696; p = 0.024; 95% CI 1.138-6.386; margin: ill-defined vs. well-defined, OR 2.685; p = 0.038; 95% CI 1.057-6.820; and intratumoral vascularity: yes vs. no, OR 3.286; p = 0.008; 95% CI 1.367-7.898) were significant independent predictors of high methylation tumors. This model had an area under the receiver operating characteristic curve (AUC) of 0.725 (95% CI 0.623-0.827).

CONCLUSIONS

Higher levels of RUNX3 methylation are associated with shorter survival in ccRCC patients. And presence of intratumoral vascularity, ill-defined margin, and left side tumor were significant independent predictors of high methylation level of RUNX3 gene.

KEY POINTS

• RUNX3 methylation level is negatively associated with overall survival in ccRCC patients. • Presence of intratumoral vascularity, ill-defined margin, and left side tumor were significant independent predictors of high methylation level of RUNX3 gene.

摘要

目的

研究 CT 成像特征、RUNX3 甲基化水平与肾透明细胞癌(ccRCC)患者生存之间的关系。

材料与方法

根据 RUNX3 甲基化水平(使用 X-tile 确定阈值),将患者分为高 RUNX3 甲基化组和低 RUNX3 甲基化组。回顾性分析 106 例 ccRCC 患者的 CT 扫描数据。采用 Kaplan-Meier 分析和 Cox 回归分析(单因素和多因素)评估 RUNX3 甲基化水平与总生存率之间的关系。采用卡方检验和逻辑回归分析(单因素和多因素)评估 RUNX3 甲基化水平与 CT 特征之间的关系。

结果

β值截距为 0.53,用于区分高甲基化(N=44)和低甲基化肿瘤(N=62)。低甲基化患者的中位总生存期更长(49.3 与 28.4 个月;低 vs. 高,调整后的危险比 [HR] 4.933,95%CI 2.054-11.852,p<0.001)。单因素逻辑回归分析显示,4 个风险因素(边界、侧位、长径和肿瘤内血管)与 RUNX3 甲基化水平相关(均 p<0.05)。多因素逻辑回归分析发现,3 个风险因素(侧位:左 vs. 右,比值比 [OR] 2.696;p=0.024;95%CI 1.138-6.386;边界:不清晰 vs. 清晰,OR 2.685;p=0.038;95%CI 1.057-6.820;肿瘤内血管:是 vs. 否,OR 3.286;p=0.008;95%CI 1.367-7.898)是高甲基化肿瘤的显著独立预测因子。该模型的受试者工作特征曲线(ROC)下面积(AUC)为 0.725(95%CI 0.623-0.827)。

结论

RUNX3 甲基化水平升高与 ccRCC 患者的总生存率降低相关。肿瘤内血管、边界不清晰和左侧肿瘤是 RUNX3 基因高甲基化的显著独立预测因子。

关键要点

  1. RUNX3 甲基化水平与 ccRCC 患者的总生存率呈负相关。

  2. 肿瘤内血管、边界不清晰和左侧肿瘤是 RUNX3 基因高甲基化的显著独立预测因子。

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