Bioinformatics analysis of KLF2 as a potential prognostic factor in ccRCC and association with epithelial-mesenchymal transition

Fangfang Hu; Yan Ren; Zunyun Wang; Hui Zhou; Yumei Luo; Minghua Wang; Faqing Tian; Jian Zheng; Juan Du; Gang Pang

doi:10.3892/etm.2022.11498

Bioinformatics analysis of KLF2 as a potential prognostic factor in ccRCC and association with epithelial-mesenchymal transition

Exp Ther Med. 2022 Jul 5;24(3):561. doi: 10.3892/etm.2022.11498. eCollection 2022 Sep.

Authors

Fangfang Hu^{1

2}, Yan Ren³, Zunyun Wang^{2

3}, Hui Zhou^{1

2}, Yumei Luo², Minghua Wang², Faqing Tian², Jian Zheng², Juan Du^{1

2}, Gang Pang³

Affiliations

¹ Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.
² The Second Affiliated Hospital, School of Medicine, The Chinese University of Hong Kong, Shenzhen, Guangdong 518172, P.R. China.
³ Department of Human Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui 230032, P.R. China.

Abstract

Clear cell renal cell carcinoma (ccRCC) is a primary pathological subtype of RCC and has poor clinical outcome. Krüppel-like factors (KLFs), which are zinc-finger proteins, may be involved in ccRCC development and progression. KLFs belong to the zinc-finger family of DNA-binding transcription factors and regulate transcription of downstream target genes. KLFs are involved in cancer development. The present study aimed to investigate the role of KLFs in ccRCC prognosis. The Cancer Genome Atlas database and multifactorial analysis showed that KLFs were widely expressed in pan-cancers and KLF2 was an independent protective factor for ccRCC prognosis. Patients with low KLF2 expression had a low survival probability and expression of KLF2 was downregulated in patients with ccRCC with high pathological grade (II + III vs. I). In addition, western blot and reverse transcription-quantitative PCR revealed that KLF2 was expressed at low levels in ccRCC cell lines and overexpression of KLF2 inhibited cell migration. In addition, KLF2 expression was negatively correlated with methylation. KLF2 expression was elevated following treatment of ccRCC cells with DNA methyltransferase inhibitor. A prognostic risk index prediction model was constructed based on multiple Cox regression. The receiver operating characteristic curve was 0.780 (area under curve >0.5). Furthermore, Gene Ontology enrichment analysis showed that 'cell adhesion' and 'junction' were negatively correlated with KLF2 and that high-risk group exhibited significantly activated 'epithelial-mesenchymal transition'. Western blot analysis showed that overexpression of KLF2 increased expression of E-cadherin, while decreasing levels of N-cadherin and vimentin. The present study highlighted the role of KLFs in ccRCC prognosis prediction and provides a research base for the search of validated prognostic biological markers for ccRCC.

Keywords: Krüppel-like factor; The Cancer Genome Atlas; clear cell renal cell carcinoma; epithelial-mesenchymal transition; prognosis.

Grants and funding

Funding: The present study was supported by grants from the Natural Science Founding of Anhui Provincial (grant no. 1808085MH247), Key Projects of Natural Science Research Projects in Anhui Universities (grant no. KJ2021A0202) and General Project of Natural Science Research Project of Anhui University (grant no. YJS20210280).