Predictive role of the overexpression for CXCR4, C-Met, and VEGF-C among breast cancer patients: A meta-analysis

Wang, Fang; Li, Shanshan; Zhao, Yueguang; Yang, Kunxian; Min-ju, Chen; Niu, Heng; Yang, Jingyu; Luo, Ying; Tang, Wenru; Sheng, Miaomiao

doi:10.1016/j.breast.2016.04.016

Cited by 25 publications

(16 citation statements)

References 33 publications

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“…There were two opposite opinions in four previous meta analyses [26–29]. In 2012, Wang J et al reported that VEGF-C expression could predict poor prognosis in BC patients, with a pooled HR of 2.164 (95% CI 1.256–3.729) for DFS and a pooled HR of 2.613 (95% CI 1.256–3.729) for OS [26].…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, Gao S et al reported that high VEGF-C expression was not associated with poor DFS (HR = 0.80, 95% CI 0.51–1.51) or OS (HR = 1.08, 95% CI 0.37–1.78) in BC patients in 2014[28]. In 2016, Wang F et al also reported that there was no significant association between high VEGF-C expression and OS (HR = 0.76, 95% CI 0.43–1.33) in BC patients [29]. The contradictory conclusions in different meta analyses leaded to great confusion on whether or not high VEGF-C expression was associated with prognosis in BC patients.…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, some studies reported that high VEGF-C expression had a significant association with favorable survival for BC patients [13, 22]. More interestingly, four relevant meta analyses provided two opposite opinions on relationship between high VEGF-C expression and clinical prognosis in BC patients [26–29]. The contradiction among these original studies and meta analyses seriously hindered the clinical utility of VEGF-C expression in BC patients.…”

Section: Introductionmentioning

confidence: 99%

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Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

Zhang¹,

Luo²,

Tang³

et al. 2016

PLoS ONE

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BackgroundThe prognostic significance of vascular endothelial growth factor C (VEGF-C) expression in breast cancer (BC) patients remains controversial. Therefore, this meta-analysis was performed to determine the prognostic significance of VEGF-C expression in BC patients.Materials and MethodsSeveral electronic databases were searched from January 1991 to August 2016. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the prognostic significance of VEGF-C expression for disease free survival (DFS) and overall survival (OS).ResultsThe present meta analysis totally included 21 eligible studies and 2828 patients with BC. The combined HRs were 1.87(95% CI 1.25–2.79, P = 0.001) for DFS and 1.96(95% CI 1.15–3.31, P = 0.001) for OS. The pooled HRs of non-Asian subgroup were 2.04(95%CI 1.36–3.05, P = 0.001) for DFS and 2.61(95%CI 1.51–4.52, P = 0.001) for OS, which were significantly higher than that of Asian subgroup. The funnel plot for publication bias was symmetrical. The further Egger's test and Begg's test did not detect significant publication bias (all P>0.05).ConclusionsThe present meta analysis strongly supported the prognostic role of VEGF-C expression for DFS and OS in BC patients, especially for patients in non-Asian countries. Furthermore, stratification by VEGF-C expression may help to optimize the treatments and the integrated managements for BC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

Zhang¹,

Luo²,

Tang³

et al. 2016

PLoS ONE

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“…[9–12,30,31] The CXCR4 gene is located on chromosome 2q2, and a synonymous polymorphism of CXCR4 (I138I) have been identified that may influence cancer risk. [13,14] Although the hypothesis of the neutral theory of molecular evolution—that some categories of mutation, like synonymous mutations, have too small an effect on fitness to be affected by natural selection—seems intuitively reasonable, over the past few decades the theory has been not applicable.…”

Section: Discussionmentioning

confidence: 99%

CXC motif chemokine receptor 4 gene polymorphism and cancer risk

Zhang

et al. 2016

Medicine

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Background:Previous epidemiological studies have reported the relationship between CXC motif chemokine receptor 4 (CXCR4) synonymous polymorphism (rs2228014), and risk of cancer, but the results remained conflicting and controversial. Therefore, this study was devised to evaluate the genetic effects of the rs2228014 polymorphism on cancer risk in a large meta-analysis.Methods:The computer-based databases (EMBASE, Web of Science, and PubMed) were searched for all relevant studies evaluating rs2228014 and susceptibility to cancer. In the analysis, pooled odds ratios (ORs) with its corresponding 95% confidence intervals (CIs) were calculated in 5 genetic models to assess the genetic risk. Egger regression and Begg funnel plots test were conducted to appraise the publication bias.Results:Data on rs2228014 polymorphism and overall cancer risk were available for 3684 cancer patients and 5114 healthy controls participating in 11 studies. Overall, a significantly increased risk of cancer was associated with rs2228014 polymorphism in homozygote model (OR = 2.01, 95% CI: 1.22–3.33) and in recessive model (OR = 1.97, 95% CI: 1.23–3.16). When stratified by ethnicity, the results were positive only in Asian populations (heterozygote model: OR = 1.36, 95% CI: 1.13–1.65; homozygote model: OR = 2.43, 95% CI: 1.21–4.91; dominant model: OR = 1.47, 95% CI: 1.13–1.90; recessive model: OR = 2.25, 95% CI: 1.13–4.48; and allele model: OR = 1.48, 95% CI: 1.10–1.99). Besides, in the subgroup analysis by source of control, the result was significant only in population-based control (homozygote model: OR = 2.39, 95% CI: 1.06–5.40; recessive model: pooled OR = 2.24, 95% CI: 1.02–4.96).Conclusion:In general, our results first indicated that the rs2228014 polymorphism in CXCR4 gene is correlated with an increased risk of cancer, especially among Asian ethnicity. Large, well-designed epidemiological studies are required to verify the current findings.

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“…Overview of meta-analysis studies on aberrant MET activation in tumor tissue as a prognostic biomarker in different types of cancer. The conflicting results of multiple trials have been evaluated in recent meta-analyses[68,69,72]. An earlier meta-analysis of HRs from 21 studies that included 6010 breast cancer patients showed that MET overexpression was related to shorter OS (HR 1.52, 95% CI 1.15-2.01) in 17 studies that included 4228 patients as well as to shorter relapse-free survival (RFS) (HR 1.60, 95% CI 1.27-2.00) in 12 studies with 3570 patients[70].…”

mentioning

confidence: 99%

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

Moosavi

Giovannetti

Saso³

et al. 2019

Critical Reviews in Clinical Laboratory Sciences

129

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Cancer is a major cause of death worldwide. MET tyrosine kinase receptor [MET, c-MET, hepatocyte growth factor (HGF) receptor] pathway activation is associated with the appearance of several hallmarks of cancer. The HGF/MET pathway has emerged as an important actionable target across many solid tumors; therefore, biomarker discovery becomes essential in order to guide clinical intervention and patient stratification with the aim of moving towards personalized medicine. The focus of this review is on how the aberrant activation of the HGF/MET pathway in tumor tissue or the circulation can provide diagnostic and prognostic biomarkers and predictive biomarkers of drug response. Many meta-analyses have shown that aberrant activation of the MET pathway in tumor tissue, including MET gene overexpression, gene amplification, exon 14 skipping and other activating mutations, is almost invariably associated with shorter survival and poor prognosis. Most meta-analyses have been performed in non-small cell lung cancer (NSCLC), breast, head and neck cancers as well as colorectal, gastric, pancreatic and other gastrointestinal cancers. Furthermore, several studies have shown the predictive value of MET biomarkers in the identification of patients who gain the most benefit from HGF/MET targeted therapies administered as single or combination therapies. The highest predictive values have been observed for response to foretinib and savolitinib in renal cancer, as well as tivantinib in NSCLC and colorectal cancer. However, some studies, especially those based on MET expression, have failed to show much value in these stratifications. This may be rooted in lack of standardization of methodologies, in particular in scoring systems applied in immunohistochemistry determinations or absence of oncogenic addiction of cancer cells to the MET pathway, despite detection of overexpression. Measurements of amplification and mutation aberrations are less likely to suffer from these pitfalls. Increased levels of MET soluble ectodomain (sMET) in circulation have also been associated with poor prognosis; however, the evidence is not as strong as it is with tissue-based biomarkers. As a diagnostic biomarker, sMET has shown its value in distinguishing cancer patients from healthy individuals in prostate and bladder cancers and in melanoma. On the other hand, increased circulating HGF has also been presented as a valuable prognostic and diagnostic biomarker in many cancers; however, there is controversy on the predictive value of HGF as a biomarker. Other biomarkers such as circulating tumor DNA (ctDNA) and tumor HGF levels have also been briefly covered. In conclusion, HGF/MET aberrations can provide valuable diagnostic, prognostic and predictive biomarkers and represent vital assets for personalized cancer therapy.

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Predictive role of the overexpression for CXCR4, C-Met, and VEGF-C among breast cancer patients: A meta-analysis

Cited by 25 publications

References 33 publications

Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

Prognostic Significance of High VEGF-C Expression for Patients with Breast Cancer: An Update Meta Analysis

CXC motif chemokine receptor 4 gene polymorphism and cancer risk

HGF/MET pathway aberrations as diagnostic, prognostic, and predictive biomarkers in human cancers

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