The Ion Channel-Related Gene Signatures Correlated With Diagnosis, Prognosis, and Individualized Treatment in Patients With Clear Cell Renal Cell Carcinoma

Abstract

Background: Early detection and precise prognostic evaluation of clear cell renal cell carcinoma (ccRCC) are crucial for patient life expectancy. Ion channel-related genes (ICRGs) are of great diagnostic and prognostic value as components that maintain the normal structure of the kidney. Therefore, we systematically explored the diagnostic, prognostic, and therapeutic value of ICRGs in ccRCC using the multi-database.Methods: RNA transcriptome profiles and clinical data of ccRCC patients were extracted and integrated from public databases including The Cancer Genome Atlas, ICGC, GEO, and E-MTAB databases. Ion channel-related genes were obtained from the literature collection. The diagnostic signature was performed using the LASSO and SVM-REF analyses. Meanwhile, the prognostic signature was conducted using the LASSO analyses. Molecular subtyping was performed using the ConsensusClusterPlus and the corresponding therapeutic targets were evaluated using the pRRophetic package. In addition, a prognostic nomogram was constructed based on the results of cox regression analyses.Results: We successfully constructed diagnostic signatures for five ICRGs and prognostic signatures for 10 ICRGs with AUC values greater than 0.7, showing good predictive performance. Based on the median risk score, we found that high-risk patients had a significantly worse prognosis. We also divided ccRCC patients into two clusters according to prognostic ICRGs, and there was a significant survival outcome between the two clusters and different sensitivity to diverse clinical therapeutic strategies. Meanwhile, we constructed a nomogram based on clinical molecules and signatures, and its predictive efficacy was better than the signature or the present tumor-node-metastasis staging system.Conclusion: In this study, we established useful signatures for early detection, prognosis evaluation, and individualized treatment for ccRCC. Moreover, KCNJ16 deserves to be explored comprehensively in the future.

Screening of genes characteristic of pancreatic cancer by LASSO regression combined with support vector machine and recursive feature elimination, and immune correlation analysis

“…11,12 Previous studies have also reported the use of SVM–REF screening for gene analysis of tumors. 13,14 In the present study, genes characteristic of pancreatic cancer screened by LASSO regression and SVM–REF were intersected to obtain the six pancreatic cancer signature genes SLPI , S100P , IFI27 , MSLN , DKK1 , and SERPINB5 . Zhang et al.…”

“…11,12 Previous studies have also reported the use of SVM-REF screening for gene analysis of tumors. 13,14 In the present study, genes characteristic of pancreatic cancer screened by LASSO regression and SVM-REF were intersected to obtain the six pancreatic cancer signature genes SLPI, S100P, IFI27, MSLN, DKK1, and SERPINB5. Zhang et al 15 previously showed that SLPI is a multifunctional protein involved in regulating immune responses, inhibiting protease activity, and blocking the transcription of proinflammatory genes through the nuclear factor-kappa B pathway.…”

An ion-channel-gene-based prediction model for head and neck squamous cell carcinoma: Prognostic assessment and treatment guidance

“…The comBat algorithm was then used to reduce the batch effects between the three datasets. We next screened and recorded 360 ion channel-related genes through an extensive literature review ( 24 – 26 ) and then intersected 330 genes downloaded from the HUGO Gene Nomenclature Committee (HGNC) database ( ), resulting in a total of 323 distinct ion channel-related genes. We analyzed these genes using univariate Cox regression to identify genes with prognostic significance for future studies.…”

Diverse functions of the inward-rectifying potassium channel Kir5.1 and its relationship with human diseases

“…↓ (Jiang et al, 2017) Clear cell renal cell carcinoma (ccRCC) ↓ (Zhu et al, 2022) Parathyroid carcinoma (PCA) ↑ (Adam et al, 2010) Prostate cancer (PCa) ↑ (Wu et al, 2020) Hepatocellular carcinoma (HCC) ↑ (Sun et al, 2022) Preterm birth (PTB) ↓ (Pereyra et al, 2019) Non-familial Brugada syndrome (BrS) KCNJ16 Ser261Gly (Juang et al, 2014) sudden infant death syndrome (SIDS) KCNJ16 R137S (Neubauer et al, 2022) The up arrow indicates the upregulation of KCNJ16 expression compared with the control group. The down arrow indicates the downregulation of KCNJ16 expression compared with the control group.…”

“…Multiple ion channels are destroyed and altered during the development of ccRCC. Therefore, exploring the alteration of ion channels in the development of ccRCC may facilitate diagnosis and evaluation and inform the corresponding treatment (Zhu et al, 2022). Abnormally elevated KCNJ16 expression may also lead to carcinogenesis.…”