术前血清c-Myc和GINS4对胃癌根治术患者预后的联合预测价值

Combined prognostic value of preoperative serum c-Myc and GINS4 in patients undergoing radical gastrectomy for gastric cancer

摘要:

背景与目的 胃癌根治术后患者预后差异显著，传统TNM分期难以全面反映肿瘤生物学异质性，亟需寻找稳定、无创的血清学预后标志物。本研究探讨术前血清细胞髓细胞瘤原癌基因（c-Myc）与GINS复合体亚基4（GINS4）水平及其联合检测对胃癌根治术患者预后的预测价值。方法 回顾性纳入2019年1月—2022年1月山东第二医科大学附属济南市第四人民医院行胃癌根治术患者180例（胃癌组），并选取同期健康体检者50名作为对照组。采用双抗体夹心酶联免疫吸附法测定（ELISA）术前血清c-Myc与GINS4水平。依据c-Myc与GINS4水平，将患者分为双高表达组、单一高表达组及双低表达组。采用Kaplan-Meier法分析不同表达组生存差异；采用Cox比例风险回归分析胃癌根治术患者预后的独立影响因素；采用ROC曲线评估各指标对预后的预测效能。结果 胃癌组血清c-Myc与GINS4水平均明显高于对照组（均P<0.001）。截至随访结束，180例胃癌患者3年总生存率为58.3%。双高表达组患者中位生存期24个月，3年生存率25.58%，明显低于单一高表达组和双低表达组（均P<0.001）。单因素分析显示，TNM分期、淋巴结转移、血清c-Myc及GINS4水平与患者预后相关（均P<0.05）。多因素Cox回归分析显示，TNM分期、c-Myc及GINS4均为影响胃癌根治术患者预后的独立危险因素（均P<0.05）。ROC曲线分析显示，TNM分期联合c-Myc与GINS4预测预后的AUC为0.875，高于各单项指标。结论 术前血清c-Myc与GINS4水平升高与胃癌根治术患者不良预后密切相关，二者联合检测具有较好的预后预测效能，可作为胃癌术后风险分层和预后评估的潜在血清学标志物。

Abstract:

Background and Aims Prognostic heterogeneity remains substantial among patients undergoing radical gastrectomy for gastric cancer, while conventional TNM staging is insufficient to fully reflect tumor biological behavior. This study aimed to investigate the prognostic value of preoperative serum c-Myc and GINS complex subunit 4 (GINS4) levels and their combined detection in patients undergoing radical gastrectomy for gastric cancer.Methods A total of 180 patients who underwent radical gastrectomy for gastric cancer between January 2019 and January 2022 at Jinan No.4 People's Hospital were retrospectively collected, and 50 healthy individuals undergoing health maintenance examination were included as controls. Serum c-Myc and GINS4 levels were measured using double-antibody sandwich ELISA. Patients were classified into double high-expression, single high-expression, and double low-expression groups according to cutoff values of c-Myc and GINS4 levels. Kaplan-Meier analysis was performed to compare survival outcomes among groups. Cox proportional hazards regression analysis was used to identify independent prognostic factors. Receiver operating characteristic (ROC) curves were constructed to evaluate predictive efficacy.Results Serum c-Myc and GINS4 levels were significantly elevated in gastric cancer patients compared with controls (both P<0.001). The overall 3-year survival rate was 58.3%. Patients in the double high-expression group had a median survival time of 24 months and a 3-year survival rate of 25.58%, which were significantly worse than those in the single high-expression and double low-expression groups (both P<0.001). Univariate analysis showed that TNM stage, lymph node metastasis, serum c-Myc level, and serum GINS4 level were associated with prognosis (all P<0.05). Multivariate Cox regression analysis identified TNM stage, c-Myc, and GINS4 as independent prognostic factors (all P<0.05). ROC analysis demonstrated that the combination of TNM stage, c-Myc, and GINS4 achieved an AUC of 0.875, which was superior to each individual indicator alone.Conclusion Elevated preoperative serum c-Myc and GINS4 levels are closely associated with poor prognosis in patients undergoing radical gastrectomy for gastric cancer. Combined detection of these two biomarkers shows favorable prognostic predictive performance and may serve as a potential serological marker for postoperative risk stratification and prognostic assessment.