Prognostic value of KLFs family genes in renal clear cell carcinoma

被引:0
|
作者
Fu, Mengru [1 ,2 ]
Du, Yuanzhuo [2 ,3 ]
Liu, Fei [1 ,2 ]
Xiao, Jun [1 ]
Zhang, Li [1 ]
Zeng, Yan [1 ]
Yang, Yujuan [1 ]
Yan, Yan [1 ,2 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Nephrol, Nanchang 330000, Jiangxi, Peoples R China
[2] Key Lab Urinary Syst Dis Jiangxi Prov, Nanchang, Peoples R China
[3] Nanchang Univ, Affiliated Hosp 1, Jiangxi Med Coll, Dept Urol, Nanchang 330000, Jiangxi, Peoples R China
来源
SCIENTIFIC REPORTS | 2024年 / 14卷 / 01期
基金
中国国家自然科学基金;
关键词
KLFs; CcRCC; Family genes; Survival prognosis; Online databases; TRANSCRIPTION FACTORS; EXPRESSION; OVERCOME;
D O I
10.1038/s41598-024-69892-5
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Numerous studies have shown that the Kr & uuml;ppel-like factors (KLFs) family of transcription factors regulate various eukaryotic physiological processes including the proliferation, differentiation, senescence, death, and carcinogenesis of animal cells. In addition, they are involved in the regulation of key biological processes such as cell cycle, DNA repair, and immune response. Current studies focus on investigating the role of KLFs in normal physiological conditions and the incidence and development of diseases. However002C the significance of KLFs family genes in clear cell renal cell carcinoma (ccRCC) remains partly understood; therefore, an in-depth investigation of their role and clinical value in this cancer is desired. The study aimed to investigate the role of KLF family genes in the incidence, development, and prognosis of ccRCC, and to identify the related potential biomarkers and therapeutic targets. The expression of KLFs in the RNA sequencing data of 613 ccRCCs from the TCGA database was analyzed using R software, and UALCAN and GEPIA assessed the expression of KLF genes in ccRCC. Real-time fluorescence quantitative PCR analysis was performed using 10 pairs of paired ccRCC sample tissues and renal cancer cell lines from the First Affiliated Hospital of Nanchang University. Overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of Kidney Clear Cell Carcinoma (KIRC) samples at differential expressions of KLFs in the TCGA database were analyzed using the R software, followed by generating a nomogram prediction model. GSCALite assessed the interactions of KLF genes with miRNAs and generated network maps. Protein interaction network maps of 50 neighboring genes associated with KLF mutations were analyzed using STRING with GO and KEGG functional enrichment analyses. The cBioPortal determined the probability of KLF gene mutations and their impact on OS and disease-free survival (DFS) in patients with ccRCC. Immune cell infiltration of KLFs was analyzed using TIMER. Finally, GSCALite was used to analyze the drug sensitivity and associated pathways of action of KLFs. Correlation validation using cellular experiments. KLF3/5/9/15 were significantly downregulated in ccRCC tissues, whereas KLF16/17 were upregulated compared with the adjacent tissues. Patients with high mRNA levels of KLF16/17 showed significantly lower OS, PFI, and DSS, whereas KLF3/5/9 showed a reverse trend. In patients with ccRCC, a significant correlation was observed between KLF mutations and OS and DSS. Furthermore, the correlation of KLF3/5/9 with immune cell infiltration was stronger than that of KLF15/16, while KLF17 was significantly associated with the Epithelial-Mesenchymal Transition (EMT) pathway. Overexpression of KLF5 inhibits the proliferative and migratory capacity of renal cancer cells (786-O and OS-RC-2), as well as their sensitivity to relevant small molecule drugs. Our research revealed the expression levels and biological significance of KLF genes in ccRCC, particularly highlighting the potential of KLF5 as a promising biomarker and therapeutic target for effective prognosis and diagnosis of ccRCC.
引用
收藏
页数:20
相关论文
共 50 条
  • [1] Prognostic value of immune-related genes in clear cell renal cell carcinoma
    Wan, Bangbei
    Liu, Bo
    Huang, Yuan
    Yu, Gang
    Lv, Cai
    [J]. AGING-US, 2019, 11 (23): : 11474 - 11489
  • [2] Prognostic value and immune infiltration of the NEK family in clear cell renal cell carcinoma
    Zhu, Yingli
    Lin, Jianfan
    Li, Yufei
    Luo, Zuojie
    [J]. MEDICINE, 2024, 103 (29)
  • [3] The prognostic value of cancer stage-associated genes in clear cell renal cell carcinoma
    Ding, Xiao-Sheng
    Hua, Yi-Chun
    Han, Bing-Xuan
    An, Juan
    Zhou, Li-Li
    Xu, Wei -Ran
    Shi, Hui
    Zheng, Xi -Xi
    Shi, Wei -Wei
    Li, Xiao-Yan
    [J]. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 2023, 15 (08): : 5145 - 5158
  • [4] Identification of microenvironment-related genes with prognostic value in clear cell renal cell carcinoma
    Zhang, Zhao
    Li, Zeyan
    Liu, Zhao
    Zhang, Xiang
    Yu, Nengwang
    Xu, Zhonghua
    [J]. JOURNAL OF CELLULAR BIOCHEMISTRY, 2020, 121 (07) : 3606 - 3615
  • [5] Prognostic and Immune Infiltration Signatures of GIMAP Family Genes in Clear Cell Renal Cell Carcinoma
    Zhang, Mengjiao
    Zhang, Xu
    Hou, Jing
    Liang, Xuemei
    Zhang, Ming
    [J]. FRONTIERS IN BIOSCIENCE-LANDMARK, 2023, 28 (11):
  • [6] Development and validation of the prognostic value of the immune-related genes in clear cell renal cell carcinoma
    Liao, Zhuangyao
    Yao, Haohua
    Wei, Jinhuan
    Feng, Zihao
    Chen, Wei
    Luo, Junhang
    Chen, Xu
    [J]. TRANSLATIONAL ANDROLOGY AND UROLOGY, 2021, 10 (04)
  • [7] Assessment for prognostic value of differentially expressed genes in immune microenvironment of clear cell renal cell carcinoma
    Yin, Xiaoxue
    Zhang, Xingming
    Liu, Zhenhua
    Sun, Guangxi
    Zhu, Xudong
    Zhang, Haoran
    Zhu, Sha
    Zhao, Jinge
    Chen, Junru
    Shen, Pengfei
    Wang, Jia
    Chen, Ni
    Zhou, Qiao
    Zeng, Hao
    [J]. AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 2020, 12 (09): : 5416 - 5432
  • [8] Prognostic Value of Metabolism-Related Genes and Immune Infiltration in Clear Cell Renal Cell Carcinoma
    Li, Hanwen
    Mo, Zengnan
    [J]. INTERNATIONAL JOURNAL OF GENERAL MEDICINE, 2021, 14 : 6885 - 6898
  • [9] Identification of genes that correlate clear cell renal cell carcinoma and obesity and exhibit potential prognostic value
    Zhou, Jiale
    Yang, Zhaolin
    Wu, Xiaorong
    Zhang, Jin
    Zhai, Wei
    Chen, Yonghui
    [J]. TRANSLATIONAL ANDROLOGY AND UROLOGY, 2021, 10 (02) : 680 - 691
  • [10] Identification of Key Genes of Prognostic Value in Clear Cell Renal Cell Carcinoma Microenvironment and a Risk Score Prognostic Model
    Zhao, Enfa
    Bai, Xiaofang
    [J]. DISEASE MARKERS, 2020, 2020