Integrative Analysis of VEGFA Gene Expression and Drug Targeting in Kidney Renal Clear Cell Carcinoma (KIRC)
Abstract
Background/Aim: Vascular endothelial growth factor A (VEGFA) plays an important role in angiogenesis and is known to have a strong association with the development of various types of cancer, including kidney renal clear cell carcinoma (KIRC). The purpose of this study was to analyse VEGFA expression in KIRC tissue, identify genes that have high expression correlation and explore the therapeutic potential of VEGFA through the identification of drugs that target it.
Methods: This study used a public data-based bioinformatics approach to evaluate VEGFA gene expression, identify genes that have similar expression patterns (co-expression) with it and examine the potential of drugs targeting VEGFA in KIRC. Data and analysis were obtained from various trusted databases, namely UALCAN, GEPIA, TCGA, TISIDB and DrugBank.
Results: VEGFA was found to be significantly higher expressed in KIRC tissue compared to normal tissue. Ten genes showed high expression correlation with VEGFA, namely RP1-261G23.7, FLT1, ZNF395, COL23A1, RP11-255M6.1, PLVAP, EXOC3L2, ESM1, EGLN3 and HIF1A-AS2. In addition, VEGFA is known to be the target of various therapeutic agents such as ranibizumab, VEGF-AS, bevasiranib, gliclazide, SNS-032, denibulin, aflibercept, ABT-510, dalteparin and chondroitin sulphate, most of which have a mechanism of action in inhibiting angiogenesis.
Conclusion: VEGFA has the potential to be an important biomarker and therapeutic target in KIRC. The combination of gene expression analysis and drug data confirms the strategic value of VEGFA in the development of more effective antiangiogenic therapies.
References
Calice-Silva V, Neyra JA, Ferreiro Fuentes A, Singer Wallbach Massai KK, Arruebo S, Bello AK, et al. Capacity for the management of kidney failure in the International Society of Nephrology Latin America region: report from the 2023 ISN Global Kidney Health Atlas (ISN-GKHA). Kidney Int Suppl (2011). 2024 Apr;13(1):43-56. doi: 10.1016/j.kisu.2024.01.001.
Lei G, Tang L, Yu Y, Bian W, Yu L, Zhou J, Li Y, Wang Y, Du J. The potential of targeting cuproptosis in the treatment of kidney renal clear cell carcinoma. Biomed Pharmacother. 2023 Nov;167:115522. doi: 10.1016/j.biopha.2023.115522.
Ren H, Chen X, Ji M, Song W, Cao L, Guo X. CRYAB is upregulated and predicts clinical prognosis in kidney renal clear cell carcinoma. IUBMB Life. 2025 Jan;77(1):e2938. doi: 10.1002/iub.2938.
Cao W, Chen HD, Yu YW, Li N, Chen WQ. Changing profiles of cancer burden worldwide and in China: a secondary analysis of the global cancer statistics 2020. Chin Med J (Engl). 2021 Mar 17;134(7):783-791. doi: 10.1097/CM9.0000000000001474.
Luo J, Yi T, Wang Y, Song W, Gao Z, Wang J, Li Y. ESM1 promote proliferation, invasion and angiogenesis via Akt/mTOR and Ras pathway in kidney renal clear cell carcinoma. Sci Rep. 2025 Feb 10;15(1):4902. doi: 10.1038/s41598-024-82400-z.
Irham LM, Amukti DP, Adikusuma W, Singh D, Chong R, Basyuni M, et al. Applied of bioinformatics in drug discovery and drug development: Bioinformatic analysis 1996-2024. BIO Web of Conf. 2024 Jan 9;148:01003. doi: 10.1051/bioconf/202414801003.
Xu T, Wei D, Yang Z, Xie S, Yan Z, Chen C, et al. ApoM suppresses kidney renal clear cell carcinoma growth and metastasis via the Hippo-YAP signaling pathway. Arch Biochem Biophys. 2023 Jul 15;743:109642. doi: 10.1016/j.abb.2023.109642.
Amukti DP, Irham LM, Surono S, El Khair R, Adikusuma W, Satria R, et al. Atherosclerosis research in the genomic era: global trends from 1983 to 2024. Bulg Cardiol. 2024 Dec 31;30(4):40–8. doi: 10.3897/bgcardio.30.e143367.
Situ Y, Xu Q, Deng L, Zhu Y, Gao R, Lei L, et al. System analysis of VEGFA in renal cell carcinoma: The expression, prognosis, gene regulation network and regulation targets. Int J Biol Markers. 2022 Mar;37(1):90-101. doi: 10.1177/17246008211063501.
Liu Y, Qu HC, Huang Y. Renal clear cell carcinoma-derived CXCL5 drives tumor-associated fibroblast formation and facilitates cancer progression. Pathol Res Pract. 2023 Apr;244:154319. doi: 10.1016/j.prp.2023.154319.
Okumura F, Joo-Okumura A, Nakatsukasa K, Kamura T. Hypoxia-inducible factor-2α stabilizes the von Hippel-Lindau (VHL) disease suppressor, Myb-related protein 2. PLoS One. 2017 Apr 10;12(4):e0175593. doi: 10.1371/journal.pone.0175593.
Roviello G, De Gennaro I, Vascotto I, Venturi G, D’Angelo A, Winchler C, et al. Hypoxia-inducible factor in renal cell carcinoma: from molecular insights to targeted therapies. Genes (Basel). 2024 Dec 24;16(1):6. doi: 10.3390/genes16010006.
Li J, Ran H, Zeng X, Yang D, Zeng X, Zhang P. Identification of HOXB9 based on comprehensive bioinformatics analysis for predicting prognosis of head and neck squamous cell carcinoma. Medicine (Baltimore). 2023 Sep 1;102(35):e35035. doi: 10.1097/MD.0000000000035035.
Sui Y, Lu K, Fu L. Prediction and analysis of novel key genes ITGAX, LAPTM5, SERPINE1 in clear cell renal cell carcinoma through bioinformatics analysis. PeerJ. 2021 Apr 20;9:e11272. doi: 10.7717/peerj.11272.
Amukti DP, Irham LM, Surono S, Adikusuma W, Chong R, El Khair R, et al. Genomic variants and epidemiology of atherosclerosis – worldwide correlation analysis and utilization of atherosclerosis gene variants for identification of drug target candidates with bioinformatics approach. Bulg Cardiol. 2024 Dec 31;30(4):108–20. doi: 10.3897/bgcardio.30.e145391.
Martinou EG, Moller-Levet CS, Angelidi AM. PBX4 functions as a potential novel oncopromoter in colorectal cancer: a comprehensive analysis of the PBX gene family. Am J Cancer Res. 2022 Feb 15;12(2):585-600.
Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK, et al. UALCAN: A portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017 Aug;19(8):649-58. doi: 10.1016/j.neo.2017.05.002.
Tang Z, Li C, Kang B, Gao G, Li C, Zhang Z. GEPIA: a web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 2017 Jul 3;45(W1):W98-W102. doi: 10.1093/nar/gkx247.
Yan L, Zhang Z, Liu Y, Ren S, Zhu Z, Wei L, et al. Anticancer activity of erianin: cancer-specific target prediction based on network pharmacology. Front Mol Biosci. 2022 Mar 17;9:862932. doi: 10.3389/fmolb.2022.862932.
Ru B, Wong CN, Tong Y, Zhong JY, Zhong SSW, Wu WC, et al. TISIDB: an integrated repository portal for tumor-immune system interactions. Bioinformatics. 2019 Oct 15;35(20):4200-2. doi: 10.1093/bioinformatics/btz210.
Gumelar G, Ulfa MM, Amukti DP, Irham LM, Yuliani S, Adikusuma W, et al. Harnessing genomic and bioinformatic data to broaden understanding of leukaemia across continents. Scr Med. 2024 Nov 1;55(6):717–25. doi: 10.5937/scriptamed55-51720.
Zhang B, Zhang L, Qi P, Pang R, Wang Z, Liu X, et al. Potential role of LPAR5 gene in prognosis and immunity of thyroid papillary carcinoma and pan-cancer. Sci Rep. 2023 Apr 10;13(1):5850. doi: 10.1038/s41598-023-32733-y.
Zhou H, Wei Q, Yang L, Gao Y. Medication rules and mechanism of topical traditional Chinese medicine for meibomian gland dysfunction-related dry eye disease. Altern Ther Health Med. 2023 Oct;29(7):126-132. PMID: 37442185.
Chen L, Yang A, Li Y, Liu X, Jiang W, Hu K. Molecular mechanism of oroxyli semen against triple-negative breast cancer verified by bioinformatics and in vitro experiments. Medicine (Baltimore). 2023 Sep 15;102(37):e34835. doi: 10.1097/MD.0000000000034835.
Humolungo DT, Anjani R, Irham LM, Sulistyani N, Ma’ruf M, Amukti DP, et al. Identification of pathogenic gene variants in carpal tunnel syndrome using bioinformatics approaches. E3S Web of Conf. 2024;501:01022.
Amukti DP, Wazni AR, Irham LM, Sulistyani N, Ma’ruf M, Adikusuma W, et al. Identifying pathogenic variants associated with Alzeimer by integrating genomic databases and bioinformatics approaches. E3S Web of Conf. 2024;501:01021.
Kotulak-Chrzaszcz A, Kiezun J, Czajkowski M, Matuszewski M, Klacz J, Krazinski BE, et al. The immunoreactivity of GLI1 and VEGFA is a potential prognostic factor in kidney renal clear cell carcinoma. BMC Cancer. 2023 Nov 14;23(1):1110. doi: 10.1186/s12885-023-11622-7.
Wang X, Zhang J, Wang Y, Tu M, Wang Y, Shi G. Upregulated VEGFA and DLL4 act as potential prognostic genes for clear cell renal cell carcinoma. Onco Targets Ther. 2018 Mar 26;11:1697-1706. doi: 10.2147/OTT.S150565.
Cuzziol CI, Castanhole-Nunes MMU, Pavarino ÉC, Goloni-Bertollo EM. MicroRNAs as regulators of VEGFA and NFE2L2 in cancer. Gene. 2020 Oct 30;759:144994. doi: 10.1016/j.gene.2020.144994.
Bo H, Cao K, Tang R, Zhang H, Gong Z, Liu Z, et al. A network-based approach to identify DNA methylation and its involved molecular pathways in testicular germ cell tumors. J Cancer. 2019 Jan 29;10(4):893-902. doi: 10.7150/jca.27491.
Mohammad Rezaei F, Hashemzadeh S, Ravanbakhsh Gavgani R, Hosseinpour Feizi M, Pouladi N, Samadi Kafil H, et al. Dysregulated KDR and FLT1 gene expression in colorectal cancer patients. Rep Biochem Mol Biol. 2019 Oct;8(3):244-52. PMID: 32274396.
Zhang SD, Leung KL, McCrudden CM, Kwok HF. The prognostic significance of combining VEGFA, FLT1 and KDR mRNA expressions in brain tumors. J Cancer. 2015 Jul 15;6(9):812-8. doi: 10.7150/jca.11975.
Wishart DS, Wu A. Using DrugBank for in silico drug exploration and discovery. Curr Protoc Bioinformatics. 2016 Jun 20;54:14.4.1-14.4.31. doi: 10.1002/cpbi.1.
Zou G, Zhang X, Wang L, Li X, Xie T, Zhao J, Yan J, Wang L, Ye H, Jiao S, Xiang R, Shi Y. Herb-sourced emodin inhibits angiogenesis of breast cancer by targeting VEGFA transcription. Theranostics. 2020 May 22;10(15):6839-53. doi: 10.7150/thno.43622.
Al-Debasi T, Al-Bekairy A, Al-Katheri A, Al Harbi S, Mansour M. Topical versus subconjunctival anti-vascular endothelial growth factor therapy (Bevacizumab, Ranibizumab and Aflibercept) for treatment of corneal neovascularization. Saudi J Ophthalmol. 2017 Apr-Jun;31(2):99-105. doi: 10.1016/j.sjopt.2017.02.008.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).