Nolen Brian, Marrangoni Adele, Velikokhatnaya Liudmila, Prosser Denise, Winans Matthew, Gorelik Elesier, Lokshin Anna
University of Pittsburgh Cancer Institute, Hillman Cancer Center, Pittsburgh, PA 15213, USA.
Gynecol Oncol. 2009 Jan;112(1):47-54. doi: 10.1016/j.ygyno.2008.09.043. Epub 2008 Nov 12.
Ovarian epithelial carcinoma can be subdivided into separate histological subtypes including clear cell, endometrioid, mucinous, and serous. These carcinoma subtypes may represent distinctive pathways of tumorigenesis and disease development. This distinction could potentially be reflected in the levels of tumor produced factors that enter into the circulation and serve as biomarkers of malignant growth. Here, we analyze levels of circulating biomarkers from a diverse set of patients diagnosed with ovarian carcinoma to identify biomarker trends and relationships associated with distinct carcinoma histotypes and divergent tumorigenic pathways.
We utilize multiplexed bead-based immunoassays to measure serum levels of a diverse array of fifty-eight biomarkers from the sera of patients diagnosed with various histological subtypes of ovarian carcinoma and benign lesions. The biomarkers studied include cancer antigens, oncogenes, cytokines, chemokines, receptors, growth and angiogenic factors, proteases, hormones, and apoptosis and adhesion related molecules. Levels of each biomarker are compared statistically across carcinoma subtypes as well as with benign cases.
A total of 21 serum biomarkers differ significantly between patients diagnosed with ovarian carcinomas and benign cases. Nine of these biomarkers are specific for carcinomas identified as clear cell, endometrioid, or mucinous in histology, while two biomarkers are specific for the serous histology. In a direct comparison of the histology groups, ten biomarkers are found to be subtype specific. Identified biomarkers include traditional and emerging tumor markers, cytokines and receptors, hormones, and adhesion- and metastasis-related proteins.
We demonstrate here that the divergent histology-based tumorigenic pathways proposed for ovarian epithelial carcinomas are associated with distinct profiles of circulating biomarkers. Continued investigation into the relationships between these factors should reveal new insights into the complex mechanisms underlying ovarian epithelial tumorigenesis.
卵巢上皮癌可细分为不同的组织学亚型，包括透明细胞型、子宫内膜样型、黏液性和浆液性。这些癌亚型可能代表肿瘤发生和疾病发展的不同途径。这种差异可能潜在地反映在进入循环系统并作为恶性生长生物标志物的肿瘤产生因子的水平上。在此，我们分析了一组诊断为卵巢癌的不同患者的循环生物标志物水平，以确定与不同癌组织学类型和不同致瘤途径相关的生物标志物趋势及关系。
我们利用基于微珠的多重免疫测定法，测量诊断为各种组织学亚型卵巢癌和良性病变患者血清中58种不同生物标志物的水平。所研究的生物标志物包括癌症抗原、癌基因、细胞因子、趋化因子、受体、生长和血管生成因子、蛋白酶、激素以及凋亡和黏附相关分子。对每种生物标志物的水平在癌亚型之间以及与良性病例进行统计学比较。
在诊断为卵巢癌的患者和良性病例之间，共有21种血清生物标志物存在显著差异。其中9种生物标志物对组织学上鉴定为透明细胞型、子宫内膜样型或黏液性的癌具有特异性，而2种生物标志物对浆液性组织学具有特异性。在组织学组的直接比较中，发现10种生物标志物具有亚型特异性。鉴定出的生物标志物包括传统和新兴的肿瘤标志物、细胞因子和受体、激素以及黏附与转移相关蛋白。
我们在此证明，为卵巢上皮癌提出的基于不同组织学的致瘤途径与循环生物标志物的不同谱相关。对这些因素之间关系的持续研究应能揭示卵巢上皮肿瘤发生复杂机制的新见解。
