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. 2023 Feb;14(1):51-59.
doi: 10.14740/wjon1520. Epub 2023 Feb 26.

Uses of Vascular Endothelial Growth Factor C as a Lung Adenocarcinoma Prognostic Biomarker

Shi Chen  1   2 , Ting Yu Pan  1   2 , Xiao Wu  1 , Tian Li  3 , Yu Wei  1 , Hai Lang He  1 , Xian Mei Zhou  1 , Qian Wang  1 , Ji Ping Zhu  1
Affiliations

Uses of Vascular Endothelial Growth Factor C as a Lung Adenocarcinoma Prognostic Biomarker

Shi Chen et al. World J Oncol. 2023 Feb.

Abstract

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and a leading cause of death worldwide. Vascular endothelial growth factor C (VEGF-C) has been identified as a prognosis prediction marker for LUAD. However, VEGF-C protein expression does not appear to significantly relate to LUAD patient survival in several studies.

Methods: We carried out a bioinformatic analysis to review the effect of VEGF-C mRNA expression on LUAD patient outcomes. GEPIA, UALCAN, TCGAportal, OncoLnc, LCE, GeneMANIA, Metascape, ImmuCellAI, and GSCA online databases were utilized. The expression levels of VEGF-C mRNA between normal tissue and LUAD tissue, overall survival (OS) analysis, function analysis, tumor microenvironment and drug sensitivity were conducted in the current study.

Results: We found that the expression level of VEGF-C mRNA was significantly lower in LUAD than normal tissue. Low expression of VEGF-C mRNA was also associated with better OS. VEGF-C expression was correlated with both NF1 and TP53 mutation status. No relationship was observed between VEGF-C and Tr1 or CD4 T-cell infiltrate scores. Additionally, VEGF-C was associated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance. The sensitivity of 5-fluorouracil was positively correlated with VEGF-C, and the sensitivity of TGX221 was negatively correlated with VEGF-C. The activity of BI-2536 and BRD-A94377914 was positively correlated with VEGF-C.

Conclusion: Novel LUAD prognostic biomarkers such as VEGF-C mRNA may aid diagnosis and treatment, and may help identify optimal LUAD populations for therapeutic treatments.

Keywords: Lung adenocarcinoma; P53; Survival; VEGF-C; mRNA.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Overall survival curves of VEGF-C in LUAD from different database (a) Ualcan. (b) GEPIA. (c) OncoLnc. (d) TCGA portal. (e) Results of meta-analysis from LCE. LUAD: lung adenocarcinoma; VEGF-C: vascular endothelial growth factor C.
Figure 2
Figure 2
(a) VEGF-C mRNA expression in LUAD (Ualcan, P = 7.41 × 10-3). (b) VEGF-C mRNA expression in LUAD (GEPIA, P < 0.05). (c) VEGF-C mRNA expression in LUAD based on stage (GEPIA, P = 0.0241). (d) VEGF-C protein expression in LUAD (Ualcan, P = 0.195). (e) VEGF-C mRNA expression between driver mutated (red) and not-mutated (gray) samples (TCGA portals). LUAD: lung adenocarcinoma; VEGF-C: vascular endothelial growth factor C.
Figure 3
Figure 3
(a) A composite gene-gene functional interaction network. (b) GO of VEGF-C in LUAD. (c) KEGG pathway of VEGF-C in LUAD. LUAD: lung adenocarcinoma; VEGF-C: vascular endothelial growth factor C.
Figure 4
Figure 4
Tr1 cells (a) and CD4 T cells (b) were correlated with OS in LUAD. Tr1 cells (c) and CD4 T cells (d) were not correlated with VEGF-C expression in LUAD. LUAD: lung adenocarcinoma; VEGF-C: vascular endothelial growth factor C.
Figure 5
Figure 5
Correlation between VEGF-C expression and drugs sensitivity from GDSC (a) and CTRP (b). VEGF-C: vascular endothelial growth factor C.
See this image and copyright information in PMC

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