Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2009 Nov 19;4(11):e7916. doi: 10.1371/journal.pone.0007916.
The complexity of the human plasma proteome represents a substantial challenge for biomarker discovery. Proteomic analysis of genetically engineered mouse models of cancer and isolated cancer cells and cell lines provide alternative methods for identification of potential cancer markers that would be detectable in human blood using sensitive assays. The goal of this work is to evaluate the utility of an integrative strategy using these two approaches for biomarker discovery.
METHODOLOGY/PRINCIPAL FINDINGS: We investigated a strategy that combined quantitative plasma proteomics of an ovarian cancer mouse model with analysis of proteins secreted or shed by human ovarian cancer cells. Of 106 plasma proteins identified with increased levels in tumor bearing mice, 58 were also secreted or shed from ovarian cancer cells. The remainder consisted primarily of host-response proteins. Of 25 proteins identified in the study that were assayed, 8 mostly secreted proteins common to mouse plasma and human cancer cells were significantly upregulated in a set of plasmas from ovarian cancer patients. Five of the eight proteins were confirmed to be upregulated in a second independent set of ovarian cancer plasmas, including in early stage disease.
CONCLUSIONS/SIGNIFICANCE: Integrated proteomic analysis of cancer mouse models and human cancer cell populations provides an effective approach to identify potential circulating protein biomarkers.
人类血浆蛋白质组的复杂性对生物标志物的发现构成了重大挑战。对癌症的基因工程小鼠模型和分离的癌细胞及细胞系进行蛋白质组学分析，为使用灵敏的检测方法在人血中检测到潜在的癌症标志物提供了替代方法。本研究的目的是评估使用这两种方法进行生物标志物发现的综合策略的实用性。
方法/主要发现：我们研究了一种策略，即将卵巢癌小鼠模型的定量血浆蛋白质组学与人类卵巢癌细胞分泌或脱落的蛋白质分析相结合。在荷瘤小鼠中发现的 106 种血浆蛋白中，有 58 种也从卵巢癌细胞中分泌或脱落。其余的主要是宿主反应蛋白。在研究中测定的 25 种蛋白质中，8 种在卵巢癌患者的一组血浆中显著上调的主要分泌蛋白在另一组独立的卵巢癌血浆中得到了证实，包括在早期疾病中。
结论/意义：癌症小鼠模型和人类癌细胞群体的综合蛋白质组学分析为识别潜在的循环蛋白生物标志物提供了一种有效的方法。
