Abstract
Lung cancer, primarily non-small-cell lung cancer (NSCLC), is the leading cause of cancer deaths in the United States and worldwide. While early detection significantly improves five-year survival, there are no reliable diagnostic tools for early detection. Several exosomal microRNAs (miRs) are overexpressed in NSCLC, and have been suggested as potential biomarkers for early detection. The present paper develops a mathematical model for early stage of NSCLC with emphasis on the role of the three highest overexpressed miRs, namely miR-21, miR-205 and miR-155. Simulations of the model provide quantitative relationships between the tumor volume and the total mass of each of the above miRs in the tumor. Because of the positive correlation between these miRs in the tumor tissue and in the blood, the results of the paper may be viewed as a first step toward establishing a combination of miRs 21, 205, 155 and possibly other miRs as serum biomarkers for early detection of NSCLC.
Highlights
Lung cancer is the leading cause of cancer-related deaths in the United States and worldwide, and non-small cell lung cancer (NSCLC) constitutes 85% of lung cancer deaths [1, 2]
Five years survival rate for NSCLC is significantly higher for those diagnosed at early stage [3], but there are no reliable tools for early detection of lung cancer
A growing body of evidence suggests that exosomal miRs may be used as serum biomarkers for prognosis of malignant tumors [5, 7]
Summary
Lung cancer is the leading cause of cancer-related deaths in the United States and worldwide, and non-small cell lung cancer (NSCLC) constitutes 85% of lung cancer deaths [1, 2]. Description EGF-EGFR concentration active MAPK concentration PI3K concentration active AKT concentration TKI concentration PTEN concentration Apaf-1-caspase 9 apoptosome concnetration cancer-shed exosome concentration exosomal miR-21 concentration (inlcuding miR-205) cellular miR-21 concentration (inlcuding miR-205) exosomal miR-155 concentration cellular miR-155 concentration cancer cells density normal healthy cells density doi:10.1371/journal.pone.0167706.t001. Description diffusion coefficient of exosomes diffusion coefficient of miR-21 diffusion coefficient of miR-155 diffusion coefficient of cancer cells diffusion coefficient of normal healthy cells directed migration coefficient λE production rate of EGF-EGFR λM production rate of MAPK λA production rate of AKT λMA activation rate of AKT by MAPK (Ras) λT production rate of TKI λP production rate of PTEN λAp production rate of Apaf-1. [47] & estimated [63,64,65,66] [67, 68] [69] & estimated [70, 71] [73] fitted [74] [74] [77] & estimated [77] & estimated [77] & estimated
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