PO.CL01.21 · 临床研究
比CA125更早发现卵巢癌复发的新型血清生物标志物
Novel serum biomarkers that detect ovarian cancer recurrence earlier than CA125
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
尽管对初次手术和化疗获得了完全临床缓解，但80%的晚期（III-IV期）卵巢癌患者会复发。血清生物标志物CA125被广泛用于监测患者复发。CA125在正常范围之外翻倍可在70%的病例中检测到复发性卵巢癌，提前时间为3至4.8个月。本文报告了可检测CA125漏检的复发、并能比CA125升高更早发现复发的新型生物标志物。复发性卵巢癌（OC）的新型生物标志物采用Olink多重邻近延伸分析法检测。在此前的一项研究中，我们筛选了>1,196个Olink生物标志物，鉴定出21个能够检测疾病复发的标志物，包括MUC16（CA125）、HE4以及19个新型候选标志物（Ren等，Cancer Research 80.16_Supplement (2020): 5144-5144）。这21个生物标志物在来自51例晚期卵巢癌患者的309份系列血清样本中进行了检测，这些患者经初次手术和化疗后达到完全临床缓解，随后以CA125监测复发，平均随访4年（范围1-8年）。在51例OC病例中，31例观察到复发，其中17例在复发时表现出CA125升高（>35 U/mL），14例复发时无CA125升高。总体上，20例在观察期内维持缓解。我们鉴定出四种生物标志物（DEFB4A、SULT1A1、TBCB和TCL1A），它们在临床确诊前三个月以上即可检测到OC复发。在生物标志物升高的病例中，TCL1A在临床复发前131天升高，TBCB提前104天，SULT1A1提前242天，DEFB4A提前265天。这四种标志物的组合在31例复发病例中检测出14例（45%），比标准临床诊断至少提前三个月。该四生物标志物组合在14例CA125阴性复发病例中识别出6例（43%），提前时间超过三个月。总之，本研究鉴定出一个四生物标志物血清检测组合，与单用CA125相比改善了OC复发的早期检测。该检测组合可为复发检测提供超过三个月的提前时间，并可检出CA125水平正常的患者。
查看英文原文 English abstract
Despite a complete clinical response to primary surgery and chemotherapy, 80% of patients with advanced stage (III-IV) ovarian cancer recur. The serum biomarker CA125 is widely used to monitor patients for recurrence. Doubling of CA125 outside the normal range detects recurrent ovarian cancer in 70% of cases with a lead time of 3 - 4.8 months. Here we report novel biomarkers that detect recurrence missed by CA125 and that detect recurrence at an earlier interval than elevation of CA125. Novel biomarkers for recurrent OC were measured with the Olink multiplexed proximity extension assay. In a previous study, >1,196 Olink biomarkers were screened to identify 21 that detected disease recurrence including MUC16 (CA125), HE4 and 19 novel candidates (Ren et al., Cancer Research 80.16_Supplement (2020): 5144-5144). The 21 biomarkers were measured in 309 serial serum samples from 51 OC patients with advanced stage ovarian cancer who had been placed in complete clinical remission with primary surgery and chemotherapy and then monitored for recurrence with CA125 for an average of 4 years (range 1 - 8).Among the 51 OC cases, recurrence was observed in 31 cases with 17 exhibiting elevated CA125 (>35 U/mL) at the time of recurrence and 14 experiencing recurrence without CA125 elevation. Overall, 20 cases remained in remission during the observation period. We identified four biomarkers (DEFB4A, SULT1A1, TBCB, and TCL1A) that detected OC recurrence more than three months prior to clinical confirmation. In cases where biomarkers increased, TCL1A was elevated 131 days, TBCB 104 days, SULT1A1 242 days and DEFB4A 265 days prior to clinical recurrence. A combination of the four markers detected 14 of 31 (45%) recurrent cases at least three months earlier than standard clinical diagnosis. The four-biomarker combination identified 6 of 14 (43%) CA125-negative recurrent cases more than three months in advance. In summary, this study identifies a four-biomarker serum panel that improves early detection of OC recurrence compared to CA125 alone. The panel offers a more than three months lead time for detection of recurrence and detected patients with normal CA125 levels.
利益披露 Disclosure
C. Qiu, None..
J. Celestino, None..
R. Rogers, None..
K. Lu, None..
E. Diamandis, None..
I. Prassas, None.