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

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


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.

World J Oncol. 2023;14(1):51-59


Lung adenocarcinoma; VEGF-C; Survival; mRNA; P53

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