SomaLogic, Inc., 2945 Wilderness Place, Boulder, CO, 80301, USA.
Boulder BioConsulting, Inc., 325 S 68th St., Boulder, CO, 80303, USA.
Sci Rep. 2023 Jul 27;13(1):12195. doi: 10.1038/s41598-023-38079-9.
Early detection of cancer is vital for the best chance of successful treatment, but half of all cancers are diagnosed at an advanced stage. A simple and reliable blood screening test applied routinely would therefore address a major unmet medical need. To gain insight into the value of protein biomarkers in early detection and stratification of cancer we determined the time course of changes in the plasma proteome of mice carrying transplanted human lung, breast, colon, or ovarian tumors. For protein measurements we used an aptamer-based assay which simultaneously measures ~ 5000 proteins. Along with tumor lineage-specific biomarkers, we also found 15 markers shared among all cancer types that included the energy metabolism enzymes glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phophate isomerase and dihydrolipoyl dehydrogenase as well as several important biomarkers for maintaining protein, lipid, nucleotide, or carbohydrate balance such as tryptophanyl t-RNA synthetase and nucleoside diphosphate kinase. Using significantly altered proteins in the tumor bearing mice, we developed models to stratify tumor types and to estimate the minimum detectable tumor volume. Finally, we identified significantly enriched common and unique biological pathways among the eight tumor cell lines tested.
早期发现癌症对于获得成功治疗的最佳机会至关重要,但一半的癌症都是在晚期才被诊断出来。因此,一种简单可靠的常规血液筛查测试将能够满足重大的未满足的医疗需求。为了深入了解蛋白质生物标志物在癌症早期检测和分层中的价值,我们测定了携带移植的人肺癌、乳腺癌、结肠癌或卵巢肿瘤的小鼠的血浆蛋白质组随时间的变化。对于蛋白质测量,我们使用了一种基于适体的测定法,该测定法可以同时测量约 5000 种蛋白质。除了与肿瘤谱系特异性生物标志物外,我们还发现了 15 种在所有癌症类型中都共有的标志物,其中包括糖酵解酶甘油醛-3-磷酸脱氢酶、葡萄糖-6-磷酸异构酶和二氢脂酰脱氢酶,以及几个维持蛋白质、脂质、核苷酸或碳水化合物平衡的重要标志物,如色氨酰 t-RNA 合成酶和核苷二磷酸激酶。我们使用在携带肿瘤的小鼠中显著改变的蛋白质,开发了用于分层肿瘤类型和估计最小可检测肿瘤体积的模型。最后,我们确定了在测试的八种肿瘤细胞系中共同存在的和独特的生物途径显著富集。