Decreased expression of TXNIP predicts poor prognosis in patients with clear cell renal cell carcinoma

Abstract

Accumulating evidence has demonstrated that thioredoxin interacting protein (TXNIP) is abnormally expressed in a variety of malignant tumors and functions as a tumor suppressor. However, the association between TXNIP and clear cell renal cell carcinoma (CCRCC) has not yet been fully elucidated. The aim of the present study was to evaluate the role of TXNIP in CCRCC using The Cancer Genome Atlas (TCGA) database. The RNA sequencing data and corresponding clinical data were collected from TCGA database. The association between TXNIP and patient clinicopathological characteristics was analyzed using analysis of variance and logistic regression. The Kaplan-Meier method and Cox proportional hazards model were used to assess the association between TXNIP and overall survival. Gene Set Enrichment Analysis (GSEA) was used to explore the associated signaling pathways. TXNIP expression was identified to be decreased in CCRCC tissues compared with normal tissues. The decreased expression of TXNIP in CCRCC was significantly associated with clinical stage [OR=0.509 for III vs. I (P=0.002); OR=0.527 for IV vs. I (P=0.012)], T stage [OR=0.552 for T3 vs. T1 (P=0.002)] and grade [OR=0.261 for G4 vs. G1 (P=0.027)]. Kaplan-Meier survival analysis indicated that cases of CCRCC with low TXNIP expression were associated with poorer prognoses compared with those with a high expression level (P=0.002). Univariate and multivariate Cox analyses indicated that TXNIP was an independent prognostic factor in CCRCC. GSEA revealed that 6 pathways exhibited significant differential enrichment in the TXNIP high-expression phenotype, including the WNT signaling pathway, the mitogen-activated protein kinase (MAPK) signaling pathway, the phosphatidylinositol signaling system, the transforming growth factor-β (TGF-β) signaling pathway, autophagy and the Janus kinase (JAK)-STAT signaling pathway. Taken together, the results of the present study indicate that TXNIP expression may be a potential prognostic marker for patients with CCRCC. In addition, the WNT signaling pathway, MAPK signaling pathway, phosphatidylinositol signaling system, TGF-β signaling pathway, autophagy and the JAK-STAT signaling pathway may be the crucial pathways regulated by TXNIP in CCRCC.

Prognostic Inflammasome‐Related Signature Construction in Kidney Renal Clear Cell Carcinoma Based on a Pan‐Cancer Landscape

“…TXNIP was commonly silenced in cancer cells due to genetic or epigenetic events [44]. In addition, a recent study revealed that downregulation of TXNIP could predict worse survival in KIRC, which is in good accordance with our results [45]. Regarding APP, current studies have demonstrated its overexpression and characteristic of oncogenes in some malignancies such as breast cancer [46], pancreatic cancer [47], and NSCLC [48].…”

FOXD1 Repression Potentiates Radiation Effectiveness by Downregulating G3BP2 Expression and Promoting the Activation of TXNIP-Related Pathways in Oral Cancer

“…In contrast, TXNIP , a member of the tumor suppressor family, has been shown to increase p53 stability and activity, thereby sensitizing breast cancer cells to apoptotic stimulation [ 48 ]. On the other hand, a recent report showed that an increased level of TXNIP probably results from the activation of the JAK-STAT pathway and is associated with a favorable prognosis in patients with renal cell carcinoma [ 49 ]. In this study, our data showed that FOXD1 knockdown dramatically enhances the expression of TXNIP and the IFN-α/γ responsiveness, which is determined by the interaction of the JAK/STAT1 signaling axis with IFN-stimulated response element (ISRE) and IFN-gamma activation site (GAS) response element within the upstream promoter of the luciferase gene in oral cancer cells.…”

A Ferroptosis-Related Gene Signature Identified as a Novel Prognostic Biomarker for Colon Cancer

“…The stress response gene ATF3 , has been shown to activate erastin-induced ferroptosis by repressing amino acid antiporter system Xc – ( Wang et al, 2020 ) and could serve as a prognostic biomarker in hepatocellular carcinoma ( Li et al, 2021 ). TXNIP has been implicated in ferroptosis in retinal cells ( Singh et al, 2020 ), and its downregulation indicates poor prognosis in patients with clear cell renal cell carcinoma ( Gao et al, 2020 ). Furthermore, ABCC1 , also known as multidrug resistance protein 1 ( MRP1 ), was confirmed to affect ferroptosis process by mediating GSH efflux ( Cao et al, 2019 ).…”