Association of Vascular Endothelial Growth Factor (<i>VEGF</i>) Gene Polymorphisms With Gastric Cancer and Its Development, Prognosis, and Survival

Liu, Weimin; Dong, Zhiyong; Hu, Ruixiang; Wang, Cunchuan

doi:10.1177/1533034617753810

Cited by 20 publications

(24 citation statements)

References 23 publications

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“…Second, due to limited number of the randomized clinical trials, sub-group analysis on the gastric cancers in terms of tumor stages, metastasis status, location of the cancer in the gastroenterological tract and ethnic difference was not performed. In this regard, it has been reported that VEGF-634 G.CC allele and GG genotype were associated with gastric cancer risk in Caucasians, while VEGF +1612G/A gen polymorphism was associated with gastric cancer risk for the Asian population, 41 and that ethnic difference was associated with outcomes of TKI treatment between Caucasian and Asian patients with malignant tumor. 48 Third, only one Phase III trial on the VEGF receptor TKI (apatinib) was enrolled and analyzed together with other studies with anti-VEGF-A mAb or anti-VEGFR mAb, and thus more randomized clinical trials data on VEGFR-TKI are necessary to confirm the benefit of selective VEGFR-TKI on gastric cancer treatment.…”

Section: Discussionmentioning

confidence: 98%

“…Most recently, a systematic review and meta-analysis indicated that VEGFR-2 over-expression is a promising negative prognosis predictor for patients with gastric cancer. 41 The REGARD 16 and RAINBOW 17 randomized Phase III clinical trials tested the efficacy of ramucirumab in advanced/metastatic pretreated gastric cancers; the primary end point (OS rate) was met in both studies. In the REGARD trial, 16 median OS was 5.2 vs 3.8 months and median PFS was 2.1 vs 1.3 months with advantage in the ramucirumab arm.…”

Section: Discussionmentioning

confidence: 99%

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A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer

Bai

Zhang

2018

OTT

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IntroductionTo date, anti-vascular endothelial growth factor (VEGF) monoclonal antibody (mAb, bevacizumab), anti-VEGF receptor mAb (ramucirumab) and selective vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (sunitinib, sorafenib and apatinib) have been tested in the clinical trials.Materials and methodsIn the current study, results of 32 clinical trials (24 Phase I or II, 8 Phase III) were systematically reviewed and meta-analysis was performed in 8 Phase III trial results.ResultsIt was found that median overall survival (OS) time and progression-free survival (PFS) time were significantly longer in the patients treated with antiangiogenic reagents compared to that in the patients with placebo when all of 8 Phase III clinical trials were analyzed together (OS: odds ratio = 0.805, 95% CI: 0.719–0.901, P < 0.001; PFS: odds ratio = 0.719, 95% CI: 0.533–969, P = 0.030).ConclusionMeta-analysis on bevacizumab (4 out 8 Phase III trials) indicated that neither OS nor PFS was significantly different between the groups treated with bevacizumab or placebo with or without combination of other chemotherapeutic reagents (OS: odds ratio = 0.909, 95% CI: 0.780–1.059, P = 0.221; PFS: odds ratio = 0.985, 95% CI: 0.865–1.122, P = 0.826). By contrast, meta-analysis on ramucirumab (3 out of 8 Phase III trials) revealed that ramucirumab was significantly favored in the treatment of gastric cancer with significant different OS between the two groups (odds ratio = 0.720, 95% CI: 0.604–0.858, P < 0.001). In addition, patients treated with VEGF or VEGFR blockers had higher morbidity of hypertension and neutropenia, but lower risk of side effects of vomiting and anemia. These findings suggest that addition of antiangiogenesis reagents, especially anti-VEGFR-mAb, to the first- or second-line chemotherapy could prolong patient’s OS and PFS time in the advanced or metastatic gastric cancer.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer

Bai

Zhang

2018

OTT

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“…A meta-analysis including these studies showed the 1612 A allele was a recessive gastric cancer susceptibility allele with a 60% increase of risk [37]. Recent meta-analysis showed + 1612 G/A G allele may decrease the gastric cancer risk in the Asian population [45, 46]. Some studies were examined for the relationship between cancer risk and − 2578 C > T and − 634G > C polymorphism [34, 48, 49].…”

Section: Discussionmentioning

confidence: 99%

“…However, Chinese study didn’t revealed association these two SNP and the gastric cancer risk [49]. Meta-analyasis revealed that VEGF− 2578 C > A gene polymorphisms were found to be unassociated with gastric cancer risk, whereas the VEGF-634 G > C GG genotype was associated with gastric cancer risk [45].…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy

et al. 2019

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Background The relationship between polymorphisms in vascular endothelial growth factor (VEGF) and gastric cancer is still inconclusive. We investigated whether there is an association between VEGF genetic polymorphisms and risk of gastric cancer, and evaluated the recurrence of advanced gastric cancer after curative resection with adjuvant chemotherapy according to VEGF genetic polymorphisms. Methods The association of functional single nucleotide polymorphisms (SNPs) of the VEGF gene (+936C > T, − 634G > C, − 2578C > A, + 1612G > A) were evaluated. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. A total of 151 patients with gastric cancer were enrolled, and the control group consisted of 413 individuals with esophago-gastroduodenoscopy who were randomly selected through health screening. All of the enrolled patients had curative resections with completion of adjuvant capecitabine and oxaliplatin combination chemotherapy and the initial metastatic cases were excluded. During the regular follow-up protocol, the episodes of the recurrence were documented and the specific genotype and allelic frequencies were evaluated. Results As for the cancer risk, there were no significant differences in specific genotypes and allelic frequencies. The mean follow-up period was 28.82 ± 30.92 (12 ~ 72) months and the recurrence rate was 28.3%. In the patients carrying the 936-C allele, the recurrence rate of gastric cancer was high ( P = 0.02). Disease-free interval was significantly different between the patients carrying the 936-CC and 936-CT/TT genotype ( P = 0.02). Conclusions VEGF 936-C allele is associated with poor prognosis, but not risk of gastric cancer. In the patients carrying the 936-C allele, more potent adjuvant treatment would be considered.

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“…The establishment of stable gradients through the binding with ECM molecules impacts on the activity of the key angiogenic factor VEGFA, which, depending on its concentration, can regulate various aspects of tumor angiogenesis [202,203]. VEGFA is upregulated in GI cancer and represents a useful prognostic and predictive biomarker [204][205][206]. In the TME, the majority of VEGFA is bound to ECM molecules as TSP-1 and -2 [175], perlecan [207], and multimerin-2 [116,117].…”

Section: Indirect Mechanismsmentioning

confidence: 99%

Role of Extracellular Matrix in Gastrointestinal Cancer-Associated Angiogenesis

Andreuzzi

Capuano

Poletto

et al. 2020

IJMS

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Gastrointestinal tumors are responsible for more cancer-related fatalities than any other type of tumors, and colorectal and gastric malignancies account for a large part of these diseases. Thus, there is an urgent need to develop new therapeutic approaches to improve the patients’ outcome and the tumor microenvironment is a promising arena for the development of such treatments. In fact, the nature of the microenvironment in the different gastrointestinal tracts may significantly influence not only tumor development but also the therapy response. In particular, an important microenvironmental component and a potential therapeutic target is the vasculature. In this context, the extracellular matrix is a key component exerting an active effect in all the hallmarks of cancer, including angiogenesis. Here, we summarized the current knowledge on the role of extracellular matrix in affecting endothelial cell function and intratumoral vascularization in the context of colorectal and gastric cancer. The extracellular matrix acts both directly on endothelial cells and indirectly through its remodeling and the consequent release of growth factors. We envision that a deeper understanding of the role of extracellular matrix and of its remodeling during cancer progression is of chief importance for the development of new, more efficacious, targeted therapies.

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Association of Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms With Gastric Cancer and Its Development, Prognosis, and Survival

Cited by 20 publications

References 23 publications

A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer

A systematic review and meta-analysis on the effect of angiogenesis blockade for the treatment of gastric cancer

Genetic polymorphisms of vascular endothelial growth factor (VEGF) associated with gastric cancer recurrence after curative resection with adjuvant chemotherapy

Role of Extracellular Matrix in Gastrointestinal Cancer-Associated Angiogenesis

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