Hao Wenrui, Friedman Avner
Mathematical Biosciences Institute, The Ohio State University, Columbus, OH, United States of America.
Department of Mathematics, The Ohio State University, Columbus, OH, United States of America.
PLoS One. 2016 Apr 14;11(4):e0153508. doi: 10.1371/journal.pone.0153508. eCollection 2016.
There are currently over 2.5 million breast cancer survivors in the United States and, according to the American Cancer Society, 10 to 20 percent of these women will develop recurrent breast cancer. Early detection of recurrence can avoid unnecessary radical treatment. However, self-examination or mammography screening may not discover a recurring cancer if the number of surviving cancer cells is small, while biopsy is too invasive and cannot be frequently repeated. It is therefore important to identify non-invasive biomarkers that can detect early recurrence. The present paper develops a mathematical model of cancer recurrence. The model, based on a system of partial differential equations, focuses on tissue biomarkers that include the plasminogen system. Among them, only uPAR is known to have significant correlation to its concentration in serum and could therefore be a good candidate for serum biomarker. The model includes uPAR and other associated cytokines and cells. It is assumed that the residual cancer cells that survived primary cancer therapy are concentrated in the same location within a region with a very small diameter. Model simulations establish a quantitative relation between the diameter of the growing cancer and the total uPAR mass in the cancer. This relation is used to identify uPAR as a potential serum biomarker for breast cancer recurrence.
目前美国有超过250万乳腺癌幸存者,据美国癌症协会称,这些女性中有10%至20%会患复发性乳腺癌。早期发现复发可避免不必要的根治性治疗。然而,如果存活的癌细胞数量很少,自我检查或乳房X光筛查可能无法发现复发性癌症,而活检具有侵入性且不能频繁重复。因此,识别能够检测早期复发的非侵入性生物标志物非常重要。本文建立了一个癌症复发的数学模型。该模型基于偏微分方程组,重点关注包括纤溶酶原系统在内的组织生物标志物。其中,只有尿激酶型纤溶酶原激活物受体(uPAR)已知与其血清浓度有显著相关性,因此可能是血清生物标志物的良好候选者。该模型包括uPAR和其他相关细胞因子及细胞。假设在原发性癌症治疗后存活的残留癌细胞集中在一个直径非常小的区域内的同一位置。模型模拟建立了生长中的癌症直径与癌症中uPAR总质量之间的定量关系。这种关系被用来确定uPAR作为乳腺癌复发的潜在血清生物标志物。