Prognostic value of neutrophil extracellular trap signature in clear cell renal cell carcinoma

Rong Li; Xuewen Jiang; Pin Wang; Xiaoyan Liu

doi:10.3389/fonc.2023.1205713

Prognostic value of neutrophil extracellular trap signature in clear cell renal cell carcinoma

Front Oncol. 2023 Jul 13:13:1205713. doi: 10.3389/fonc.2023.1205713. eCollection 2023.

Authors

Rong Li¹, Xuewen Jiang², Pin Wang³, Xiaoyan Liu¹

Affiliations

¹ Phase I Clinical Trial Center, Qilu Hospital of Shandong University, Jinan, China.
² Department of Urology, Qilu Hospital of Shandong University, Jinan, China.
³ National Health Commission (NHC) Key Laboratory of Otorhinolaryngology, Department of Otorhinolaryngology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, China.

Abstract

Introduction: Clear cell renal cell carcinoma (ccRCC) is the most prevalent type of urological carcinoma. Although targeted therapy and immunotherapy are usually employed, they often result in primary and acquired resistance. There is currently a lack of dependable biomarkers that can accurately anticipate the prognosis of ccRCC. Recent research has indicated the critical role of neutrophil extracellular traps (NETs) in the development, metastasis, and immune evasion of cancer. The aim of this study was to explore the value of NETs in the development and prognosis of ccRCC.

Methods: Clinical features and genetic expression information of ccRCC patients were acquired from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and E-MTAB-1980 database. NETs-related gene set were obtained from previous studies. A NETs-related gene signature was constructed based on TCGA data and validated using ICGC and E-MTAB-1980 databases. Furthermore, the immune microenvironment and responsiveness to anticancer medications in ccRCC patients with varying levels of NETs risks were investigated.

Results: A total of 31 NET-related genes were differently expressed between normal kidney and ccRCC tissues. 17 out of 31 were significantly associated with overall survival. After LASSO Cox regression analysis, nine NETs-related genes were enrolled to construct the NETs prognosis signature, and all the ccRCC patients from TCGA were divided into low and high risk group. This signature demonstrated excellent performance in predicting the overall survival of TCGA patients as well as the validation ICGC and E-MTAB-1980 patients. Additionally, the NETs signature was significantly correlated with immune infiltration and drug sensitivity.

Conclusions: The NETs signature established by the current study has prognostic significance in ccRCC, and may serve as a useful biomarker for patient stratification and treatment decisions. Further validation and clinical studies are required to fully translate these findings into clinical practice.

Keywords: clear cell renal cell carcinoma; immune microenvironment; multiomics data; neutrophil extracellular traps; prognosis signature; therapy sensitivity; validation.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81902585) and Natural Science Foundation of Shandong Province (ZR2022MH313).