Long non-coding RNAs enable precise diagnosis and prediction of early relapse after nephrectomy in patients with renal cell carcinoma

Abstract

Purpose Renal cell carcinoma belongs among the deadliest malignancies despite great progress in therapy and accessibility of primary care. One of the main unmet medical needs remains the possibility of early diagnosis before the tumor dissemination and prediction of early relapse and disease progression after a successful nephrectomy. In our study, we aimed to identify novel diagnostic and prognostic biomarkers using next-generation sequencing on a novel cohort of RCC patients. Methods Global expression profiles have been obtained using next-generation sequencing of paired tumor and non-tumor tissue of 48 RCC patients. Twenty candidate lncRNA have been selected for further validation on an independent cohort of paired tumor and non-tumor tissue of 198 RCC patients. Results Sequencing data analysis showed significant dysregulation of more than 2800 lncRNAs. Out of 20 candidate lncRNAs selected for validation, we confirmed that 14 of them are statistically significantly dysregulated. In order to yield better discriminatory results, we combined several best performing lncRNAs into diagnostic and prognostic models. A diagnostic model consisting of AZGP1P1, CDKN2B-AS1, COL18A1, and RMST achieved AUC 0.9808, sensitivity 95.96%, and specificity 90.4%. The model for prediction of early relapse after nephrectomy consists of COLCA1, RMST, SNHG3, and ZNF667-AS1 and achieved AUC 0.9241 with sensitivity 93.75% and specificity 71.07%. Notably, no combination has outperformed COLCA1 alone. Lastly, a model for stage consists of ZNF667-AS1, PVT1, RMST, LINC00955, and TCL6 and achieves AUC 0.812, sensitivity 85.71%, and specificity 69.41%. Conclusion In our work, we identified several lncRNAs as potential biomarkers and developed models for diagnosis and prognostication in relation to stage and early relapse after nephrectomy.

Methylation-driven mechanisms of allergic rhinitis during pollen and non-pollen seasons using integrated bioinformatics analysis

“…lncRNAs were proven to play an integral role in the pathogenesis of allergic disease by regulating the differentiation and apoptosis of hematopoietic stem cells, bone marrow cells, and the activation of monocytes, macrophages, and dendritic cells in immune regulation ( Cheng et al, 2022 ). ZNF667-AS1 has been the focus of recent research on inflammatory conditions and cancer with an emphasis on its function in the control of inflammatory pathways ( Di Fiore et al, 2021 ; Zheng et al, 2021 ; Fan et al, 2022 ; Luan et al, 2022 ; Ma et al, 2022 ; Bohosova et al, 2023 ). Excitingly, we discovered that Liu et al's bioinformatics study ( Liu et al, 2019 ), based on data GSE67472, identified ZNF667-AS1 as an important gene involved in the pathogenesis of asthma, which is also downregulated in asthma.…”