摘要
目的:以ALU247与ALU115质量浓度比值定义的血清循环DNA（cfDNA）完整性的检测方法，探讨其联合血清肿瘤标志物在胃癌首次诊治及预后的价值。方法:收集蚌埠医学院第一附属医院2020年12月至2023年6月收治的79例胃癌患者（胃癌组）血液及同期年龄构成相对应的39名健康体检者（对照组）的外周血，检测cfDNA的两个不同长度基因片段（ALU115和ALU247）质量浓度，并计算ALU247/ALU115比值，得到血清cfDNA完整性。比较两组CEA、CA19-9、CA724、CA125、cfDNA完整性水平，观察cfDNA完整性与胃癌临床病理参数的关系，绘制受试者工作特征（ROC）曲线，分析并比较CEA、CA19-9、CA724、CA125、ALU247/ALU115比值（cfDNA完整性）和5项指标联合检测对胃癌早期的诊断效能；对患者进行随访，分析cfDNA完整性与胃癌患者预后的关系。结果:根据最大约登指数，CEA、CA19-9、CA724、CA125、ALU247/ALU115比值和联合检测的cut-off值分别为4.56、15.42、0.32、14.74、0.41、0.50时，作为诊断指标的曲线下面积（AUC）分别为0.53、0.70、0.71、0.61、0.83、0.90，cfDNA完整性单独作为胃癌肿瘤标志物的特异度高于传统肿瘤标志物，但敏感度低于CA724，当联合检测时，敏感度明显升高，但特异度稍有降低。cfDNA完整性与胃癌患者生存时间无明显关系（P=0.129）。结论:血清cfDNA完整性联合传统血清肿瘤标志物检测在胃癌的首次诊断中具有一定的临床意义，基于cfDNA浓度以及完整性的液体活检有望成为胃癌的新型检测方法。
Abstract
Objective:To detect the integrity of cell-free DNA (cfDNA) in serum defined by the ratio of ALU247 to ALU115 content, and to investigate its clinical value and prognostic value in the first diagnosis and treatment of gastric cancer (GC) in combination with serum tumor markers.Methods:The blood samples of 79 GC patients (GC group) admitted to the First Affiliated Hospital of Bengbu Medical College from December 2020 to June 2023 and the peripheral blood samples from 39 healthy individuals (control group) with corresponding age composition during the same period were collected, the contents of two different lengths of cfDNA (ALU115 and ALU247) were detected, and the ratio of ALU247/ALU115 were calculated to obtain the integrity of their serum cfDNA. The levels of CEA, CA19-9, CA724, CA125 and ALU247/ALU115 between the two groups were compared, the relationship between cfDNA integrity and the clinicopathological parameters of GC was observed, and the receiver operating characteristics (ROC) curve of the subjects was plotted to analyze and compare the diagnostic efficacy of CEA, CA19-9, CA724, CA125, ALU247/ALU115 and the combined test for the early stage of GC. Patients were followed up to analyze the relationship between cfDNA integrity and the prognosis.Results:According to the maximum Jordon’s index, the area under the curve (AUC) of CEA, CA19-9, CA724, CA125, ALU247/ALU115 and combined detection as diagnostic indexes were 0.53, 0.70, 0.71, 0.61, 0.83, 0.90, when the cut-off values of the above index were selected as 4.56, 15.42, 0.32, 14.74, 0.41, 0.50 respectively. The specificity of cfDNA integrity as a tumor marker alone was higher than that of traditional tumor markers, but the sensitivity was lower than that of CA724. The sensitivity was significantly higher when cfDNA integrity was detected in combination with traditional serum tumor markers, but the specificity was slightly lower. There was no significant relationship between cfDNA integrity and survival time of GC patients (P=0.129).Conclusion:The combination of serum cfDNA integrity and traditional serum tumor markers has certain clinical significance in the first diagnosis of GC, and liquid biopsy based on the concentration and integrity of cfDNA is expected to become a new detection method for GC.
基金项目
安徽省高校自然科学研究项目(KJ2021A0765)
万方数据