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Identification of urine protein biomarkers with the potential for early detection of lung cancer.

Zhang H, Cao J, Li L, Liu Y, Zhao H, Li N, Li B, Zhang A, Huang H, Chen S, Dong M, Yu L, Zhang J, Chen L - Sci Rep (2015)

Bottom Line: Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls.Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients.These tumor biomarkers could potentially aid in the early detection of lung cancer.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science, Tsinghua University, Beijing 100084, China.

ABSTRACT
Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.

No MeSH data available.


Related in: MedlinePlus

Schematic diagram of the experimental design.Urine samples from paired control and tumor-bearing mice and paired lung cancer patients/healthy controls were subjected to LC-MS analysis. Up-regulated protein candidates common to patients and tumor-bearing mice were identified. Western blotting and ELISA were used to validate the candidate proteins in an independent cohort of clinical samples.
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f1: Schematic diagram of the experimental design.Urine samples from paired control and tumor-bearing mice and paired lung cancer patients/healthy controls were subjected to LC-MS analysis. Up-regulated protein candidates common to patients and tumor-bearing mice were identified. Western blotting and ELISA were used to validate the candidate proteins in an independent cohort of clinical samples.

Mentions: Drastic changes in expression and functioning in oncogenes and tumor suppressor gene are prominent features of tumor181920. A marked alteration in both gene and protein expression between normal and cancerous cells is reflected in alterations of the proteomic profiles of the body fluids of cancer patients212223. Currently, biomarker identification in peripheral body fluids is achieved by comparing proteomic patterns between patients and healthy controls. Unfortunately, differences in genetic backgrounds, environments and lifestyles between healthy individuals and patients result in a high level of noise in proteomic signals, and because of this high noise level, it is difficult to identify protein markers of in vivo tumor burden. We hypothesize that only a few up-regulated urine proteins are capable of identifying lung cancer tumor burdens; we termed this group of proteins the urine “signature” of lung tumor burdens. However, compared with the urine of healthy controls, patients’ urine contains not only this signature of up-regulated proteins but also many other proteins that reflect differences in genetic backgrounds, environments and lifestyles. By contrast, GEMMs feature pure genetic backgrounds and strictly controlled environments that minimize noise that obscures the identification of urine biomarkers for lung cancer. By identifying up-regulated proteins that are common to both tumor-bearing mice and patients, we maximize our chance of identifying actual tumor signature proteins in urine. Thus, we propose a procedure for efficient identification of urine biomarkers, shown in the schematic in Fig. 1.


Identification of urine protein biomarkers with the potential for early detection of lung cancer.

Zhang H, Cao J, Li L, Liu Y, Zhao H, Li N, Li B, Zhang A, Huang H, Chen S, Dong M, Yu L, Zhang J, Chen L - Sci Rep (2015)

Schematic diagram of the experimental design.Urine samples from paired control and tumor-bearing mice and paired lung cancer patients/healthy controls were subjected to LC-MS analysis. Up-regulated protein candidates common to patients and tumor-bearing mice were identified. Western blotting and ELISA were used to validate the candidate proteins in an independent cohort of clinical samples.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488871&req=5

f1: Schematic diagram of the experimental design.Urine samples from paired control and tumor-bearing mice and paired lung cancer patients/healthy controls were subjected to LC-MS analysis. Up-regulated protein candidates common to patients and tumor-bearing mice were identified. Western blotting and ELISA were used to validate the candidate proteins in an independent cohort of clinical samples.
Mentions: Drastic changes in expression and functioning in oncogenes and tumor suppressor gene are prominent features of tumor181920. A marked alteration in both gene and protein expression between normal and cancerous cells is reflected in alterations of the proteomic profiles of the body fluids of cancer patients212223. Currently, biomarker identification in peripheral body fluids is achieved by comparing proteomic patterns between patients and healthy controls. Unfortunately, differences in genetic backgrounds, environments and lifestyles between healthy individuals and patients result in a high level of noise in proteomic signals, and because of this high noise level, it is difficult to identify protein markers of in vivo tumor burden. We hypothesize that only a few up-regulated urine proteins are capable of identifying lung cancer tumor burdens; we termed this group of proteins the urine “signature” of lung tumor burdens. However, compared with the urine of healthy controls, patients’ urine contains not only this signature of up-regulated proteins but also many other proteins that reflect differences in genetic backgrounds, environments and lifestyles. By contrast, GEMMs feature pure genetic backgrounds and strictly controlled environments that minimize noise that obscures the identification of urine biomarkers for lung cancer. By identifying up-regulated proteins that are common to both tumor-bearing mice and patients, we maximize our chance of identifying actual tumor signature proteins in urine. Thus, we propose a procedure for efficient identification of urine biomarkers, shown in the schematic in Fig. 1.

Bottom Line: Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls.Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients.These tumor biomarkers could potentially aid in the early detection of lung cancer.

View Article: PubMed Central - PubMed

Affiliation: School of Life Science, Tsinghua University, Beijing 100084, China.

ABSTRACT
Lung cancer is the leading cause of cancer-related deaths and has an overall 5-year survival rate lower than 15%. Large-scale clinical trials have demonstrated a significant relative reduction in mortality in high-risk individuals with low-dose computed tomography screening. However, biomarkers capable of identifying the most at-risk population and detecting lung cancer before it becomes clinically apparent are urgently needed in the clinic. Here, we report the identification of urine biomarkers capable of detecting lung cancer. Using the well-characterized inducible Kras (G12D) mouse model of lung cancer, we identified alterations in the urine proteome in tumor-bearing mice compared with sibling controls. Marked differences at the proteomic level were also detected between the urine of patients and that of healthy population controls. Importantly, we identified 7 proteins commonly found to be significantly up-regulated in both tumor-bearing mice and patients. In an independent cohort, we showed that 2 of the 7 proteins were up-regulated in urine samples from lung cancer patients but not in those from controls. The kinetics of these proteins correlated with the disease state in the mouse model. These tumor biomarkers could potentially aid in the early detection of lung cancer.

No MeSH data available.


Related in: MedlinePlus