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The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

Kim YW, Yun SJ, Jeong P, Kim SK, Kim SY, Yan C, Seo SP, Lee SK, Kim J, Kim WJ - PLoS ONE (2015)

Bottom Line: In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis.In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients.These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.

ABSTRACT
Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier curves showing that high expression of PDGFRL (one of the PDGFR isoforms) correlates with disease progression in NMIBC patients.
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pone.0134552.g004: Kaplan–Meier curves showing that high expression of PDGFRL (one of the PDGFR isoforms) correlates with disease progression in NMIBC patients.

Mentions: Next, to understand the clinical relevance of increased PDGFR expression in BCa, we examined the clinical correlation between PDGFR isoform expression and disease progression. We found that PDGFRL expression was significantly correlated with NMIBC progression (p = 0.046; HR, 3.675; 95% CI, 1.024–13.188) (Table 5). KM survival analysis showed that NMIBC patients with high expression of PDGFRL showed poorer PFS than those with low expression of PDGFRL (log-rank test, p = 0.032) (Fig 4).


The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

Kim YW, Yun SJ, Jeong P, Kim SK, Kim SY, Yan C, Seo SP, Lee SK, Kim J, Kim WJ - PLoS ONE (2015)

Kaplan–Meier curves showing that high expression of PDGFRL (one of the PDGFR isoforms) correlates with disease progression in NMIBC patients.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4520492&req=5

pone.0134552.g004: Kaplan–Meier curves showing that high expression of PDGFRL (one of the PDGFR isoforms) correlates with disease progression in NMIBC patients.
Mentions: Next, to understand the clinical relevance of increased PDGFR expression in BCa, we examined the clinical correlation between PDGFR isoform expression and disease progression. We found that PDGFRL expression was significantly correlated with NMIBC progression (p = 0.046; HR, 3.675; 95% CI, 1.024–13.188) (Table 5). KM survival analysis showed that NMIBC patients with high expression of PDGFRL showed poorer PFS than those with low expression of PDGFRL (log-rank test, p = 0.032) (Fig 4).

Bottom Line: In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis.In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients.These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, College of Medicine, Chungbuk National University, Cheongju, South Korea.

ABSTRACT
Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

No MeSH data available.


Related in: MedlinePlus