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. 2022 Jul 6;44(7):3075-3088.
doi: 10.3390/cimb44070212.

The Expression and Prognostic Significance of VEGF and CXCR4 in Gastric Cancer: Correlation with Angiogenesis, Lymphangiogenesis and Progression

Łukasz Kruszyna  1 , Dawid Murawa  2 , Paweł Piotr Jagodziński  3 , Grzegorz Oszkinis  4 , Zbigniew Krasiński  1
Affiliations

The Expression and Prognostic Significance of VEGF and CXCR4 in Gastric Cancer: Correlation with Angiogenesis, Lymphangiogenesis and Progression

Łukasz Kruszyna et al. Curr Issues Mol Biol. .

Abstract

The cellular response to hypoxia includes the expression of hypoxia-inducible factor-1 (HIF-1) and its target genes: vascular endothelial growth factor (VEGF) and CXC chemokine receptor 4 (CXCR4). The aim of this study was to investigate the expression and prognostic significance of VEGF and CXCR4, which are responsible for angiogenesis and progression in gastric cancer. Twenty-eight gastric cancer patients were analyzed. The mRNA expression was examined in primary tumors and corresponding normal gastric mucosa by RT-PCR. The protein level was examined by immunohistochemistry staining. The high expression of VEGF and CXCR4 was found in 71.0 and 64.0% of tumors, respectively. The mean levels of VEGF and CXCR4 were upregulated in primary tumors compared to normal mucosa (p = 0.0007, p = 0.0052). A correlation between VEGF expression and tumor invasion (p = 0.0216) and stage (p = 0.0181) was found. CXCR4 expression correlated with lymph node metastases (p = 0.0237) and stage (p = 0.0054). The VEGF expression correlated with microvessel density (MVD) (p = 0.0491). The overall 3-year survival rate was 46.4% and correlated negatively with high CXCR4 mRNA expression (p = 0.0089). VEGF and CXCR4 play an important role in tumor progression. Their overexpression correlates with a bad prognosis and may improve high-risk patient selection, and these patients may obtain additional survival benefits if treated more aggressively.

Keywords: CXCR4; VEGF; angiogenesis; gastric cancer; lymph node metastases; lymphangiogenesis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The expression level of VEGF mRNA (a) and CXCR4 mRNA (b) in primary tumors, corresponding normal gastric mucosa and control tissue. Data are presented as mean ± SEM; * difference in mRNA expression between cancer and corresponding normal mucosa (Wilcoxon test); ** difference in mRNA expression between cancer and control tissue (Mann–Whitney U test).
Figure 2
Figure 2
Relationship between mean mRNA expression of VEGF and CXCR4 according to the depth of tumor invasion (pT) (a,b); lymph node metastases (pN) (c,d) and stage (e,f). Data are presented as mean ± SEM; * p < 0.05; Mann–Whitney test.
Figure 3
Figure 3
Immunohistological staining for VEGF and CD34 in primary gastric cancer samples. Positive staining was observed as a brown color. Representative examples of low (+), moderate (++), and strong (+++) expression (magnification 200×).
Figure 4
Figure 4
The 3-year overall survival in patients with surgically resected gastric cancer (a). The Kaplan–Meier survival curves according to the level of VEGF mRNA (b) and CXCR4 (c) expression in gastric cancer tissues; log-rank test.
See this image and copyright information in PMC

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References

    1. Bray F., Ferlay J., Soerjomataram I., Siegel R.L., Torre L.A., Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018;68:394–424. doi: 10.3322/caac.21492. - DOI - PubMed
    1. Lordick F., Allum W., Carneiro F., Mitry E., Tabernero J., Tan P., Van Cutsem E., van de Velde C., Cervantes A. Unmet needs and challenges in gastric cancer: The way forward. Cancer Treat. Rev. 2014;40:692–700. doi: 10.1016/j.ctrv.2014.03.002. - DOI - PubMed
    1. Miyahara R., Niwa Y., Matsuura T., Maeda O., Ando T., Ohmiya N., Itoh A., Hirooka Y., Goto H. Prevalence and prognosis of gastric cancer detected by screening in a large Japanese population: Data from a single institute over 30 years. J. Gastroenterol. Hepatol. 2007;22:1435–1442. doi: 10.1111/j.1440-1746.2007.04991.x. - DOI - PubMed
    1. Mizokami K., Kakeji Y., Oda S., Irie K., Yonemura T., Konishi F., Maehara Y. Clinicopathologic significance of hypoxia-inducible factor 1alpha overexpression in gastric carcinomas. J. Surg. Oncol. 2006;94:149–154. doi: 10.1002/jso.20568. - DOI - PubMed
    1. Chen W.T., Huang C.J., Wu M.T., Yang S.F., Su Y.C., Chai C.Y. Hypoxia-inducible factor-1alpha is associated with risk of aggressive behavior and tumor angiogenesis in gastrointestinal stromal tumor. Jpn J. Clin. Oncol. 2005;35:207–213. doi: 10.1093/jjco/hyi067. - DOI - PubMed