Research Paper Volume 15, Issue 20 pp 11313—11330

Role of NF-κB pathway in kidney renal clear cell carcinoma and its potential therapeutic implications

Jiaao Sun1, , Feng Chen1, , Guangzhen Wu1, ,

  • 1 Department of Urology, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China

Received: July 14, 2023       Accepted: October 2, 2023       Published: October 16, 2023      

https://doi.org/10.18632/aging.205129
How to Cite

Copyright: © 2023 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Kidney renal clear cell carcinoma (KIRC), a common malignant tumor of the urinary system, is the most aggressive renal tumor subtype. Since the discovery of nuclear factor kappa B (NF-κB) in 1986, many studies have demonstrated abnormal NF-κB signaling is associated with the development of various cancers, including kidney renal clear cell carcinoma. In this study, the relationship between NF-κB and kidney renal clear cell carcinoma was confirmed using bioinformatics analysis. First, we explored the differential expression of copy number variation (CNV), single nucleotide variant (SNV), and messenger RNA (mRNA) in NF-κB-related genes in different types of cancer, as well as the impact on cancer prognosis and sensitivity to common chemotherapy drugs. Then, we divided the mRNA expression levels of NF-κB-related genes in KIRC patients into three groups through GSVA cluster analysis and explored the correlation between the NF-κB pathway and clinical data of KIRC patients, classical cancer-related genes, common anticancer drug responsiveness, and immune cell infiltration. Finally, 11 tumor-related genes were screened using least absolute shrinkage and selection operator (LASSO) regression to construct a prognostic model. In addition, we used the UALCAN and HPA databases to verify the protein levels of three key NF-κB-related genes (CHUK, IKGGB, and IKBKG) in KIRC. In conclusion, our study established a prognostic survival model based on NF-κB-related genes, which can be used to predict the prognosis of patients with KIRC.

Abbreviations

RCC: Renal cell carcinoma; KIRC: Kidney renal clear cell carcinoma; RHD: Rel homology domain; IκB: Inhibitor of κB; IKK: Inhibitor of κB kinase; MMP: Matrix metalloproteinase; HCC: Hepatocellular carcinoma; VEGF: Vascular endothelial growth factor; ACC: Adrenocortical carcinoma; BLCA: Bladder Urothelial Carcinoma; BRCA: Breast invasive carcinoma; CESC: Cervical squamous cell carcinoma; CHOL: Cholangiocarcinoma; COAD: Colon adenocarcinoma; DLBC: Lymphoid Neoplasm Diffuse Large B-cell Lymphoma; ESCA: Esophageal carcinoma; GBM: Glioblastoma multiforme; GBML: Glioma; HNSC: Head and Neck squamous cell carcinoma; KICH: Kidney chromophobe; KIRP: Kidney renal papillary cell carcinoma; LAML: Acute myeloid leukemia; LGG: Brain lower-grade glioma; LIHC: Liver hepatocellular carcinoma; LUAD: Lung adenocarcinoma; LUSC: Lung squamous cell carcinoma; MESO: Mesothelioma; OV: Ovarian serous cystadenocarcinoma; PAAD: Pancreatic adenocarcinoma; PCPG: Pheochromocytoma and paraganglioma; PRAD: Prostate adenocarcinoma; READ: Rectum adenocarcinoma; SARC: Sarcoma; SKCM: Skin cutaneous melanoma; STAD: Stomach adenocarcinoma; STES: Stomach and esophageal carcinoma; TGCT: Testicular germ cell tumors; THCA: Thyroid carcinoma; THYM: Thymoma; UCEC: Uterine corpus endometrial carcinoma; UCS: Uterine carcinosarcoma; UVM: Uveal melanoma; CDK6: Cyclin-dependent kinase 6.