van Agthoven Ton, Eijkenboom Wil M H, Looijenga Leendert H J
Department of Pathology, Laboratory for Experimental Patho-Oncology, Erasmus MC Cancer Institute, Be-432A, P.O. Box 2040, 3000 CA, Rotterdam, NL, The Netherlands.
Cell Oncol (Dordr). 2017 Aug;40(4):379-388. doi: 10.1007/s13402-017-0333-9. Epub 2017 Jun 13.
α-fetoprotein (AFP) and human chorionic gonadotropin subunit beta (B-HCG) are informative serum biomarkers for the primary diagnosis and follow-up of testicular germ cell cancer (TGCC) patients. About 20% of TGCC patients with a non-seminoma (NS) and about 80% with a seminoma (SE) are, however, negative for these biomarkers. Embryonic stem cell microRNAs (miRs) may serve as promising alternative serum biomarkers. Here we investigated a retrospective series of serum samples from selected TGCC patients who developed a relapse in time to test the possible additional value of the serum-based ampTSmiR test compared to the conventional serum-based protein biomarkers for follow-up.
We investigated 261 retrospective serum samples of six selected fully evaluated TGCC patients with a proven relapse using the ampTSmiR test for miR-371a-3p, miR-373-3p, and miR-367-3p and compared the results to those of the conventional protein biomarkers.
At primary diagnosis, elevated serum B-HCG, AFP and LDH levels were found to be informative in 4/6, 3/6 and 3/6 patients, respectively. At primary diagnosis the levels of miR-371a-3p and miR-373-3p were elevated in 4/4, and miR-367-3p in 3/4 patients. For two cases no starting serum sample was available for retrospective miR analysis. Residual disease (overlooked by histopathological examination) was detected in one case by miR-371a-3p only. The miR-371a-3p level was increased in one patient two months before detection of an intracranial metastasis. B-HCG was informative in 3/4 and the ampTSmiR test in 4/4 patients with a relapse or residual disease. None of the biomarkers were informative for the detection of residual mature teratoma.
The ampTSmiR test is more sensitive than the conventional TGCC protein biomarkers for the detection of residual disease and relapse, excluding mature teratoma.
甲胎蛋白(AFP)和人绒毛膜促性腺激素β亚基(β-HCG)是睾丸生殖细胞癌(TGCC)患者初步诊断及后续监测的重要血清生物标志物。然而,约20%的非精原细胞瘤(NS)TGCC患者和约80%的精原细胞瘤(SE)TGCC患者这些生物标志物呈阴性。胚胎干细胞微小RNA(miR)可能是很有前景的替代血清生物标志物。在此,我们对部分TGCC复发患者的一系列血清样本进行回顾性研究,以检测基于血清的ampTSmiR检测相较于传统基于血清的蛋白质生物标志物在后续监测中的潜在附加价值。
我们使用ampTSmiR检测对6例经充分评估且复发得到证实的选定TGCC患者的261份回顾性血清样本进行miR-371a-3p、miR-373-3p和miR-367-3p检测,并将结果与传统蛋白质生物标志物的结果进行比较。
在初步诊断时,血清β-HCG、AFP和乳酸脱氢酶(LDH)水平升高分别在4/6、3/6和3/6的患者中具有诊断意义。在初步诊断时,4/4患者的miR-371a-3p和miR-373-3p水平升高,3/4患者的miR-367-3p水平升高。有2例患者没有起始血清样本用于回顾性miR分析。仅通过miR-371a-3p在1例患者中检测到残留疾病(组织病理学检查遗漏)。1例患者在检测到颅内转移前两个月miR-371a-3p水平升高。3/4复发或残留疾病患者的β-HCG检测具有诊断意义,4/4患者的ampTSmiR检测具有诊断意义。没有一种生物标志物对残留成熟畸胎瘤的检测具有诊断意义。
ampTSmiR检测在检测残留疾病和复发(不包括成熟畸胎瘤)方面比传统的TGCC蛋白质生物标志物更敏感。