Rogmans Christoph, Kuhlmann Jan Dominik, Hugendieck Gerrit, Link Theresa, Arnold Norbert, Weimer Jörg Paul, Flörkemeier Inken, Rambow Anna-Christina, Lieb Wolfgang, Maass Nicolai, Bauerschlag Dirk O, Hedemann Nina
Department of Gynecology and Obstetrics, Christian-Albrechts-University Kiel and University Medical Center Schleswig-Holstein Campus Kiel, 24105 Kiel, Germany.
Department of Gynecology and Obstetrics, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01219 Dresden, Germany.
Cancers (Basel). 2021 Nov 6;13(21):5563. doi: 10.3390/cancers13215563.
Ovarian cancer has the highest mortality rate among gynecological tumors. This is based on late diagnosis and the lack of early symptoms. To improve early detection, it is essential to find reliable biomarkers. The metalloprotease ADAM17 could be a potential marker, as it is highly expressed in many solid tumors, including ovarian and breast cancer. The aim of this work is to evaluate the relevance of ADAM17 as a potential diagnostic blood-based biomarker in ovarian cancer. Ovarian cancer cell lines IGROV-1 and A2780, as well as primary patient-derived tumor cells obtained from tumor tissue and ascitic fluid, were cultured to analyze ADAM17 abundance in the culture supernatant. In a translational approach, a cohort of 117 well-characterized ovarian cancer patients was assembled and ADAM17 levels in serum and corresponding ascitic fluid were determined at primary diagnosis. ADAM17 was quantified by enzyme-linked immunosorbent assay (ELISA). In the present study, ADAM17 was detected in the culture supernatant of ovarian cancer cell lines and primary cells. In addition, ADAM17 was found in serum and ascites of ovarian cancer patients. ADAM17 level was significantly increased in ovarian cancer patients compared to an age-matched control group ( < 0.0001). Importantly early FIGO I/II stages, which would not have been detected by CA-125, were associated with higher ADAM17 concentrations ( = 0.007). This is the first study proposing ADAM17 as a serum tumor marker in the setting of a gynecological tumor disease. Usage of ADAM17 in combination with CA-125 and other markers could help detect early stages of ovarian cancer.
卵巢癌在妇科肿瘤中死亡率最高。这是由于诊断较晚且缺乏早期症状。为了改善早期检测,找到可靠的生物标志物至关重要。金属蛋白酶ADAM17可能是一种潜在标志物,因为它在包括卵巢癌和乳腺癌在内的许多实体瘤中高表达。这项工作的目的是评估ADAM17作为卵巢癌潜在的基于血液的诊断生物标志物的相关性。培养卵巢癌细胞系IGROV-1和A2780,以及从肿瘤组织和腹水获得的原发性患者来源的肿瘤细胞,以分析培养上清液中ADAM17的丰度。在一项转化研究中,收集了117例特征明确的卵巢癌患者队列,并在初次诊断时测定血清和相应腹水中的ADAM17水平。通过酶联免疫吸附测定(ELISA)对ADAM17进行定量。在本研究中,在卵巢癌细胞系和原代细胞的培养上清液中检测到ADAM17。此外,在卵巢癌患者的血清和腹水中也发现了ADAM17。与年龄匹配的对照组相比,卵巢癌患者的ADAM17水平显著升高(<0.0001)。重要的是,FIGO I/II期早期(CA-125无法检测到)与较高的ADAM17浓度相关(=0.007)。这是第一项提出将ADAM17作为妇科肿瘤疾病血清肿瘤标志物的研究。将ADAM17与CA-125和其他标志物联合使用可能有助于检测卵巢癌的早期阶段。