卵巢上皮性癌患者血清无细胞DNA的检测及临床意义

Detection of serum cell-free DNA in patients with epithelial ovarian carcinoma and its clinical significance

目的:检测循环无细胞DNA中的肿瘤相关cfDNA(ALU247/ALU115)及CA-125基因片段(CA125-cfDNA)在卵巢上皮性癌患者血清中的表达,探讨其是否可作为卵巢上皮性癌早期诊断及病情监测的指标。方法:采用半定量RT-PCR方法检测48例卵巢上皮性癌、16例良性卵巢上皮性肿瘤和12例正常健康对照血清中游离的ALU247、ALU115、CA125、β-actin DNA片段的表达。结果:卵巢上皮性癌患者血清中的肿瘤相关cfDNA(ALU247/ALU115)和CA125-cfDNA的相对水平(CA125-cfDNA/β-actin)明显高于卵巢良性肿瘤患者、正常对照及术后化疗二疗程者的值,晚期患者(Ⅲ-Ⅳ期)血清中的表达明显高于早期患者(Ⅰ-Ⅱ期),早期患者的表达明显高于正常对照组(P<0.05),该两项指标与病理学类型及病理分级无关。CA125-cfDNA的相对水平与血清CA125的值存在相关性,在晚期卵巢上皮性癌未化疗患者腹水中的值显著高于血清中的值(P<0.05)。结论:检测血清中ALU247/ALU115及CA125-cfDNA基因片段的水平可作为血清CA125的有效补充指标,用于卵巢上皮性肿瘤良恶性鉴别诊断、早期诊断和病情监测。

Objective：To detect the tumor related cell-free DNA （ALU247/ALU115 ）and CA125 gene fragment （CA125 cell-free DNA, CA125-cfDNA） in the serum of patients with epithelial ovarian carcinoma （EOC） and to investigate the values of CA125-cfDNA for early diagnosis and prognosis in EOC. Methods：Semi-quantitative PCR was used to analyze the level of the serum cfDNA ineluding ALU247, ALU115, CA125-cfDNA and β-actin in 48 patients with epithelial ovarian carcinoma （EOC）, 16 patients with benign ovarian tumor, and 12 normal controls. Results：The relative values of serum tumor related cfDNA and CA125-cfDNA in the preoperative patients with EOC were significantly higher than those with benign ovarian disease, the healthy control subjects, and the patients who received postoperative two-cycle chemotherapy. The relative values of serum tumor related cfDNA and CA125-cfDNA were significantly higher in advanced EOC patients at stage Ⅲ-Ⅳ than those with early EOC at stage Ⅰ - Ⅱ （ P 〈 0.05 ）, and significantly higher in early EOC patients than healthy controls （ P 〈 0.05 ）. There were no significant correlations of the serum levels of tumor related cfDNA and CA125-cfDNA with pathological classification and histological grade （ P 〉 0.05 ）. The relative value of serum CA125-cfDNA was associated with serum CA125 level. The level was much higher in ascites than that in the serum from the patients with advanced EOC （P 〈 0.05 ）. Conclusion：The detection of cfDNA （ALU247/ALU115 ） and CA125-cfDNA in serum may be used as assistant markers in addition to serum CA125 level for differential and early diagnosis of EOC as well as monitoring the change of EOC.