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p53 自身抗体作为浆液性卵巢癌潜在的检测和预后生物标志物。

p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer.

机构信息

Cancer Vaccine Center, Department of Medical Oncology, Dana-Farber Cancer Institute, HIM416, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

出版信息

Cancer Epidemiol Biomarkers Prev. 2010 Mar;19(3):859-68. doi: 10.1158/1055-9965.EPI-09-0880. Epub 2010 Mar 3.

Abstract

BACKGROUND

This study examined the value of serum p53 autoantibodies (p53-AAb) as detection and prognostic biomarkers in ovarian cancer.

METHODS

p53-AAb were detected by ELISA in sera obtained preoperatively from women undergoing surgery for a pelvic mass. This group included women subsequently diagnosed with invasive serous ovarian cancer (n = 60), nonserous ovarian cancers (n = 30), and women with benign disease (n = 30). Age-matched controls were selected from the general population (n = 120). Receiver operating characteristic curves were constructed to compare the values of p53-AAb, CA 125, and HE4 as a screening biomarker. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess its prognostic value on survival.

RESULTS

p53-AAb were detected in 25 of 60 (41.7%) of serous cases, 4 of 30 (13.3%) nonserous cases, 3 of 30 (10%) benign disease cases, and 10 of 120 (8.3%) controls (combined P = 0.0002). p53-AAb did not significantly improve the detection of cases [area under the curve (AUC), 0.69] or the discrimination of benign versus malignant disease (AUC, 0.64) compared with CA 125 (AUC, 0.99) or HE4 (AUC, 0.98). In multivariate analysis among cases, p53-AAb correlated only with a family history of breast cancer (P = 0.01). Detectable p53 antibodies in pretreatment sera were correlated with improved overall survival (P = 0.04; hazard ratio, 0.57; 95% confidence interval, 0.33-0.97) in serous ovarian cancer.

CONCLUSIONS

Antibodies to p53 are detected in the sera of 42% of patients with advanced serous ovarian cancer.

IMPACT

Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.

摘要

背景

本研究探讨了血清 p53 自身抗体(p53-AAb)作为卵巢癌检测和预后生物标志物的价值。

方法

通过酶联免疫吸附试验(ELISA)检测术前接受盆腔肿块手术的女性血清中的 p53-AAb。该组包括随后被诊断为侵袭性浆液性卵巢癌(n=60)、非浆液性卵巢癌(n=30)和良性疾病(n=30)的女性。年龄匹配的对照组从普通人群中选择(n=120)。构建受试者工作特征曲线以比较 p53-AAb、CA125 和 HE4 作为筛查生物标志物的价值。使用 Kaplan-Meier 曲线和 Cox 比例风险模型评估其对生存的预后价值。

结果

在 60 例浆液性病例中,25 例(41.7%)、30 例非浆液性病例中 4 例(13.3%)、30 例良性疾病病例中 3 例(10%)和 120 例对照组中 10 例(8.3%)检测到 p53-AAb(总 P=0.0002)。与 CA125(AUC,0.99)或 HE4(AUC,0.98)相比,p53-AAb 并未显著提高病例的检出率(曲线下面积(AUC),0.69)或良性与恶性疾病的鉴别能力(AUC,0.64)。在病例的多变量分析中,p53-AAb 仅与乳腺癌家族史相关(P=0.01)。治疗前血清中可检测到的 p53 抗体与浆液性卵巢癌患者的总生存改善相关(P=0.04;风险比,0.57;95%置信区间,0.33-0.97)。

结论

在 42%的晚期浆液性卵巢癌患者的血清中检测到 p53 抗体。

影响

尽管其作为术前诊断生物标志物的效用,除了 CA125 和 HE4 之外,是有限的,但 p53-AAb 是总生存改善的预后因素。

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