Identification of immune-related genes as prognostic factors in bladder cancer

Abstract

Bladder cancer is one of the most common cancers worldwide. The immune response and immune cell infiltration play crucial roles in tumour progression. Immunotherapy has delivered breakthrough achievements in the past decade in bladder cancer. Differentially expressed genes and immune-related genes (DEIRGs) were identified by using the edgeR package. Gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed for functional enrichment analysis of DEIRGs. Survival-associated IRGs were identified by univariate Cox regression analysis. A prognostic model was established by univariate COX regression analysis, and verified by a validation prognostic model based on the GEO database. Patients were divided into high-risk and low-risk groups based on the median risk score value for immune cell infiltration and clinicopathological analyses. A regulatory network of survival-associated IRGs and potential transcription factors was constructed to investigate the potential regulatory mechanisms of survival-associated IRGs. Nomogram and ROC curve to verify the accuracy of the model. Quantitative real-time PCR was performed to validate the expression of relevant key genes in the prognostic model. A total of 259 differentially expressed IRGs were identified in the present study. KEGG pathway analysis of IRGs showed that the “cytokine-cytokine receptor interaction” pathway was the most significantly enriched pathway. Thirteen survival-associated IRGs were selected to establish a prognostic index for bladder cancer. In both TCGA prognostic model and GEO validation model, patients with high riskscore had worse prognosis compared to low riskscore group. A high infiltration level of macrophages was observed in high-risk patients. OGN, ELN, ANXA6, ILK and TGFB3 were identified as hub survival-associated IRGs in the network. EBF1, WWTR1, GATA6, MYH11, and MEF2C were involved in the transcriptional regulation of these survival-associated hub IRGs. The present study identified several survival-associated IRGs of clinical significance and established a prognostic index for bladder cancer outcome evaluation for the first time.

A novel immune-related RNA-binding proteins signature to predict survival and therapeutic responses in prostate cancer

“…The function and role of ZC3HAV1L in tumors are unknown, and this study confirms for the first time the prognostic value of this gene in prostate cancer. OGN could induce bone formation by interacting with TGF and is highly associated with prognosis in multitype cancer [22][23][24][25]. The transcription factor NFIC can bind to the promoter region of OGN and promote the transcriptional activity of OGN, which in turn inhibits the NF-κB signaling pathway and suppresses the ability of proliferation in bladder cancer [26].…”

HYAL3 as a potential novel marker of BLCA patient prognosis

“…In addition, IDUA is a novel glycolysisrelated gene that is associated with the immune microenvironment in renal cell carcinoma [24]. Moreover, ELN has been reported to be an immune-related gene in BLCA [25]. HYAL3 was associated with several GO functions, including androgen receptor signaling, response to oxidative stress, and negative regulation of the target of rapamycin signaling, the latter of which might correlate with immunocyte infiltration [26][27][28].…”

Evaluation of Annexins Family as Potential Biomarker for Predicting Progression and Prognosis in Clear Renal Cell Carcinoma

“…ANXA6 is highly expressed in a variety of tumours, such as acute myeloid leukaemia [38], bladder cancer [39], and breast carcinoma [40]. However, its expression and prognostic role in KIRC have not been reported.…”