We aimed to assess the effect of VEGF-A, PDGF-BB, and c-Met expression levels on survival in patients with metastatic colorectal cancer receiving bevacizumab therapies.
Patients and methods
A total of 105 patients diagnosed with metastatic colorectal cancer between the years 2006 and 2016 were included in the research retrospectively.
Results
The progression-free survival (PFS) durations of patients with high expression levels of VEGF-A and with low expression levels of VEGF-A were 11 months and 10 months (p = 0.44), respectively. The PFS durations of patients with high PDGF-BB expression and low PDGF-BB expression were 12 months and 10 months (p = 0.16), respectively, while the PFS durations of patients with high and low c-Met expression were 8 months and 13 months (p = 0.005), respectively. Metastatic overall survival was 27 months and 18 months (p = 0.05) in patients with high and low VEGF-A expression levels, respectively, 31 months and 21 months (p = 0.16) in patients with high and low PDGF-BB expression levels, respectively, and 21 months and 26 months (p = 0.11) in patients with high and low c-Met expression levels, respectively.
Conclusion
The results of this research revealed a high c-Met expression relationship with worse PFS and low VEGF-A expression associated with poor metastatic overall survival in patients with metastatic colorectal cancer receiving bevacizumab therapies.
HeinemannVvon WeikersthalLFDeckerT, et al.
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. Lancet Oncol2014;
15: 1065–1075.
2.
CohenDJHochsterHS.Update on clinical data with regimens inhibiting angiogenesis and epidermal growth factor receptor for patients with newly diagnosed metastatic colorectal cancer. Clin Colorectal Cancer2007;
7: S21–S27.
3.
KerbelRS.Tumorangiogenesis. N Engl J Med2008;
358: 2039–2049.
4.
FerraraNHouckKJakemanL, et al.
Molecular and biological properties of the vascular endothelial growth factor family of proteins. Endocr Rev1992;
13: 18–32.
5.
CulyC.Bevacizumab: antiangiogenic cancer therapy.Drugs Today (Barc)2005;
41: 23–36.
6.
PietrasKRubinKSjöblomT, et al.
Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy.Cancer Res2002;
62: 5476–5484.
7.
GastaldiSSassiFAccorneroP, et al.
Met signaling regulates growth, repopulating potential and basal cell-fate commitment of mammary luminal progenitors: implications for basal-like breast cancer. Oncogene2013;
32: 1428–1440.
8.
ChengNBhowmickNAChytilA, et al.
Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Oncogene2005 Jul 28;
24: 5053–5068.
9.
LeeSJLeeJParkSH, et al.
c-MET overexpression in colorectal cancer: a poor prognostic factor for survival. Clin Colorectal Cancer2018;
17: 165–169.
10.
StockmannCSchadendorfDKloseR, et al.
The impact of the immune system on tumor: angiogenesis and vascular remodeling.Front Oncol2014;
4: 69.
11.
MartinsSFGarciaEALuzMA, et al.
Clinicopathological correlation and prognostic significance of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression in colorectal cancer. Cancer Genom Proteom2013;
10: 55–67.
12.
CumpănasAACimpeanAMFericianO, et al.
The involvement of PDGF-B/PDGFRβ axis in the resistance to antiangiogenic and antivascular therapy in renal cancer. Anticancer Res2016;
36: 2291–2295.
13.
InancMOzkanMKaracaH, et al.
Cytokeratin 5/6, c-Met expressions, and PTEN loss prognostic indicators in triple-negative breast cancer. Med Oncol2014;
31: 801.
14.
EisenhauerEATherassePBogaertsJ, et al.
New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer2009;
45: 228–247.
15.
StintzingSModestDPRossiusL, et al.
FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab for metastatic colorectal cancer (FIRE-3): a post-hoc analysis of tumour dynamics in the final RAS wild-type subgroup of this randomized open-label phase 3 trial.Lancet Oncol2016;
17: 1426–1434.
16.
HurwitzHITebbuttNCKabbinavarF, et al.
Efficacy and safety of bevacizumab in metastatic colorectal cancer: pooled analysis from seven randomized controlled trials. Oncologist2013;
18: 1004–1012.
17.
DuranAOKaracaHBesirogluM, et al.
XELOX plus bevacizumab vs. FOLFIRI plus bevacizumab treatment for first-line chemotherapy in metastatic colon cancer: a retrospective study of the Anatolian Society of Medical Oncology. Asian Pac J Cancer Prev2014;
15: 10375–10379.
18.
AkbulutHAltuntasFAkbulutKG, et al.
Prognostic role of serum vascular endothelial growth factor, basic fibroblast growth factor and nitric oxide in patients with colorectal carcinoma. Cytokine2002;
20: 184–190.
19.
InançMErOKaracaH, et al.
Prognostic value of tumor growth factor levels during chemotherapy in patients with metastatic colorectal cancer. Med Oncol2012;
29: 3119–124.
20.
MohamedSYMohammedHLIbrahimHM, et al.Role of VEGF, CD105, and CD31 in the prognosis of colorectal cancer cases. J Gastrointest Cancer 2019; 50: 23–34.
21.
BerkVDenizKBozkurtO, et al.
Predictive significance of VEGF and HIF-1α expression in patients with metastatic colorectal cancer receiving chemotherapy combinations with bevacizumab. Asian Pac J Cancer Prev2015;
16: 6149–6154.
22.
HägglöfCHammarstenPJosefssonA, et al.
Stromal PDGFR beta expression in prostate tumors and non-malignant prostate tissue predicts prostate cancer survival. PLoSOne2010;
5: e10747.
23.
NakamuraYTanakaFYoshikawaY, et al.
PDGF-BB is a novel prognostic factor in colorectal cancer. Ann Surg Oncol2008;
15: 2129–2136.
24.
JanssonSAaltonenKBendahlPO, et al.
The PDGF pathway in breast cancer is linked to tumour aggressiveness, triple-negative subtype and early recurrence. Breast Cancer Res Treat2018;
169: 231–241.
25.
TsaoASWeiWKuhnE, et al.
Immunohistochemical overexpression of platelet-derived growth factor receptor-beta (PDGFR-β) is associated with PDGFRB gene copy number gain in sarcomatoid non-small-cell lung cancer. Clin Lung Cancer2011;
12: 369–374.
26.
FironMShaharabanyMAltstockRT, et al.
Dominant negative met reduces tumorigenicity-metastasis and increases tubule formation in mammary cells. Oncogene2000;
19: 2386–2397.
27.
PengJQiSWangP, et al.
Diagnosis and prognostic significance of c-Met in cervical cancer: a meta-analysis.Dis Markers2016;
2016: 6594016.
28.
XuYPengZLiZ, et al.
Expression and clinical significance of c-Met in advanced esophageal squamous cell carcinoma. BMC Cancer2015;
15: 6.
29.
BellDFerrarottoRFoxMD, et al.
Analysis and significance of c-MET expression in adenoid cystic carcinoma of the salivary gland. Cancer Biol Ther2015;
16: 834–838.
30.
ChenBLiuJWangX, et al.
Co-expression of PDGF-B and VEGFR-3 strongly correlates with poor prognosis in hepatocellular carcinoma patients after hepatectomy. Clin Res Hepatol Gastroenterol2018;
42: 126–133.
