TCGA Database-Based Screening of Tumor Microenvironment Immunomodulators Related to Bladder Cancer Prognosis.

OBJECTIVE: Bladder cancer (BC), as the most common malignant tumor of the urinary tract, has a complex biological behavior. Currently, there are still some limitations in the diagnosis and treatment of BC. Despite the great progress made in immunotherapy, there is still a lack of key genes for the diagnosis of BC. Therefore, it is particularly important to explore the differentially expressed genes (DEGs) and their effectiveness on prognosis of BC with different tumor microenvironment scores. METHODS: The gene expression dataset of BC was downloaded from the Cancer Genome Atlas (TCGA) database. The correlation between clinicopathological characteristics of patients and scores of immune and stromal components was analyzed. Patients were divided into high and low score groups according to their tumor microenvironment score (Immune score, Stromal score, ESTIMATE score). DEGs between high and low score groups were identified using R software and then subjected to enrichment analyses to assess their potential biological functions and signaling pathways. The protein-protein interaction (PPI) network was constructed using the STRING database to further identify hub genes. The expression levels of hub genes in BC were verified by TCGA database. Subsequently, the hub genes were evaluated for overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and disease-specific survival (DSS), and corresponding forest plots were created. RESULTS: A total of 2346 DEGs were obtained, including 1120 up-regulated genes and 1226 down-regulated genes. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses found DEGs were mainly enriched in cell migration and immune-related pathways. Meanwhile, The PPI network finally yielded top 10 hub genes with predictive value, which included actin beta (ACTB), interleukin 6 (IL-6), Jun proto-oncogene (JUN), CD4 molecule (CD4), heat shock protein 90 alpha family class A member 1 (HSP90AA1), protein tyrosine phosphatase receptor type C (PTPRC), tumor protein p53 (TP53), SRC proto-oncogene (SRC), fibronectin 1 (FN1), and tumor necrosis factor (TNF). Among them, CD4, PTPRC, and SRC were potential protective factors for BC. CONCLUSION: The top 10 hub genes (ACTB, IL-6, JUN, CD4, HSP90AA1, PTPRC, TP53, SRC, FN1, TNF) obtained based on tumor microenvironment scores all had potential predictive value. Elevated expression of protective factors (CD4, PTPRC, and SRC) indicates better survival outcome of BC subjects. Further exploration of the molecular developmental mechanisms of these hub genes will help to develop novel personalized therapies and improve BC prognosis.

Enhanced expression of TWIK-related arachidonic acid-activated K+ channel in the spinal cord of detrusor overactivity rats after partial bladder outlet obstruction.

BACKGROUND: Detrusor overactivity (DO) secondary to partial bladder outlet obstruction (PBOO) is closely associated with alteration of ion channels. The objective of this study is to investigate the expression of the TWIK-related arachidonic acid-activated K(+) channel (TRAAK) in the L6-S1 spinal cord of DO rats after PBOO. METHODS: Female Sprague-Dawley rats undergoing PBOO surgery were screened for DO by cystometry. Sham-operated rats served as controls. The expression of TRAAK in the L6-S1 spinal cord was detected by real-time polymerase chain reaction, western blotting and immunohistochemistry. RESULTS: DO was successfully induced after chronic PBOO in rats, with an incidence rate of 62.5 %. Compared with sham-operated rats, the expression of TRAAK in the L6-S1 spinal cord of DO rats was significantly increased at the mRNA (1.886 ± 0.710 versus 0.790 ± 0.679, P < 0.05) and protein level (0.510 ± 0.087 versus 0.255 ± 0.107, P < 0.05). Immunohistochemical staining showed increased expression of TRAAK in the dorsal horn and ventral horn of the spinal cord. CONCLUSIONS: Upregulation of TRAAK was observed in the spinal cord of DO rats after chronic PBOO, which may exert a protective effect against DO by suppressing the excitability of neurons.

Downregulation of TWIK-related arachidonic acid-activated K+ channel in the spinal cord of rats after complete bladder outlet obstruction.

OBJECTIVES: To study the altered expression of TWIK-related arachidonic acid-activated K(+) channel in the L6-S1 spinal cord of rats after complete bladder outlet obstruction, and to investigate the role of TWIK-related arachidonic acid-activated K(+) channel in the neurogenic mechanism of bladder dysfunction. METHODS: Female Sprague-Dawley rats were randomly divided into a complete bladder outlet obstruction group and a sham-operated control group. Cystometry was carried out and tissues of L6-S1 spinal cord were obtained for detection of TWIK-related arachidonic acid-activated K(+) channel mRNA and protein by real-time polymerase chain reaction, western blot and immunohistochemistry. RESULTS: The bladder outlet obstruction rat model was established. Real-time polymerase chain reaction, western blot and immunohistochemistry showed that the expression of TWIK-related arachidonic acid-activated K(+) channel was lower in the L6-S1 spinal cord of the bladder outlet obstruction rats, compared with the control rats. CONCLUSIONS: Downregulation of TWIK-related arachidonic acid-activated K(+) channel might enhance the excitability of the neurons and increase the sensitivity of the bladder, probably providing a new study model of overactive bladder secondary to bladder outlet obstruction.