GPR160 is a potential biomarker associated with prostate cancer.
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ABSTRACT:
SUBMITTER: Guo W
PROVIDER: S-EPMC8225807 | biostudies-literature | 2021 Jun
REPOSITORIES: biostudies-literature
Publications
GPR160 is a potential biomarker associated with prostate cancer.
Guo Wanjing W Zhang Junyu J Zhou Yan Y Zhou Caihong C Yang Yunjie Y Cong Zhaotong Z Dong Jibin J Yang Dehua D Dai Bo B Wang Ming-Wei MW
Signal transduction and targeted therapy 20210625 1
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Project description:UnlabelledProstate cancer is the second most common form of cancer in males, affecting one in eight men by the time they reach the age of 70 years. Current diagnostic tests for prostate cancer have significant problems with both false negatives and false positives, necessitating the search for new molecular markers. A recent investigation of endosomal and lysosomal proteins revealed that the critical process of endosomal biogenesis might be altered in prostate cancer. Here, a panel of endosomal markers was evaluated in prostate cancer and nonmalignant cells and a significant increase in gene and protein expression was found for early, but not late endosomal proteins. There was also a differential distribution of early endosomes, and altered endosomal traffic and signaling of the transferrin receptors (TFRC and TFR2) in prostate cancer cells. These findings support the concept that endosome biogenesis and function are altered in prostate cancer. Microarray analysis of a clinical cohort confirmed the altered endosomal gene expression observed in cultured prostate cancer cells. Furthermore, in prostate cancer patient tissue specimens, the early endosomal marker and adaptor protein APPL1 showed consistently altered basement membrane histology in the vicinity of tumors and concentrated staining within tumor masses. These novel observations on altered early endosome biogenesis provide a new avenue for prostate cancer biomarker investigation and suggest new methods for the early diagnosis and accurate prognosis of prostate cancer.ImplicationsThis discovery of altered endosome biogenesis in prostate cancer may lead to novel biomarkers for more precise cancer detection and patient prognosis.
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Project description:Prostate cancer (CaP) is the most common type of tumour disease in men. Early diagnosis of cancer of the prostate is very important, because the sooner the cancer is detected, the better it is treated. According to that fact, there is great interest in the finding of new markers including amino acids, proteins or nucleic acids. Prostate specific antigen (PSA) is commonly used and is the most important biomarker of CaP. This marker can only be detected in blood and its sensitivity is approximately 80%. Moreover, early stages cannot be diagnosed using this protein. Currently, there does not exist a test for diagnosis of early stages of prostate cancer. This fact motivates us to find markers sensitive to the early stages of CaP, which are easily detected in body fluids including urine. A potential is therefore attributed to the non-protein amino acid sarcosine, which is generated by glycine-N-methyltransferase in its biochemical cycle. In this review, we summarize analytical methods for quantification of sarcosine as a CaP marker. Moreover, pathways of the connection of synthesis of sarcosine and CaP development are discussed.
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Project description:BackgroundProstate cancer (PCa) is one of the most lethal cancers in male individuals. The synaptosome associated protein 25 (SNAP25) gene is a key mediator of multiple biological functions in tumors. However, its significant impact on the prognosis in PCa remains to be elucidated.MethodsWe performed a comprehensive analysis of the Cancer Genome Atlas dataset (TCGA) to identify the differentially expressed genes between PCa and normal prostate tissue. We subjected the differentially expressed genes to gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional analysis, and constructed a protein-protein interaction network. We then screened for pivotal genes to identify the hub genes of prognostic significance by performing Cox regression analysis. We identified SNAP25 as one such gene and analyzed the relationship between its expression in PCa to poor prognosis using GEPIA interactive web server.ResultsTCGA database demonstrated that SNAP25 was significantly downregulated in PCa. The progressive decrease in SNAP25 expression with the increase in the clinical staging and grading of PCa demonstrates that reduced SNAP25 expression considerably exacerbates the clinical presentation. Our findings confirm that SNAP25 expression strongly correlates with overall survival, which was determined using the Gleason score. We also validated the role of SNAP25 expression in the prognosis of patients with PCa. We used Gene Set Enrichment and Gene Ontology analyses to evaluate the function of SNAP25 and further explored the association between SNAP25 expression and tumor-infiltrating immune cells using the Tumor Immune Assessment Resource database. We found for the first time that SNAP25 is involved in the activation, differentiation, and migration of immune cells in PCa. Its expression was positively correlated with immune cell infiltration, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells, macrophages, and natural killer cells. SNAP25 expression also positively correlated with chemokines/chemokine receptors, suggesting that SNAP25 may regulate the migration of immune cells. In addition, our experimental results verified the low expression of SNAP25 in PCa cells.ConclusionOur findings indicate a relationship between SNAP25 expression and PCa, demonstrating that SNAP25 is a potential prognostic biomarker due to its vital role in immune infiltration.
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Project description:Introduction Prostate cancer (PC) is one of the most frequently diagnosed cancers in males. MiR-153, as a member of the microRNA (miRNA) family, plays an important role in PC. This study aims to explore the expression and possible molecular mechanisms of the miR-153 action. Methods Formalin-fixed paraffin-embedded (FFPE) tissues were collected from prostatectomy specimens of 29 metastatic and 32 initial stage PC patients. Expression levels of miR-153 were measured using real-time reverse transcription polymerase chain reaction (qRT-PCR). 2−ΔΔCT method was used for quantitative gene expression assessment. The candidate target genes for miR-153 were predicted by TargetScan. Mutations in target genes of miR-153 were identified using exome sequencing. Protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential molecular mechanisms of miR-153 in PC. Results MiR-153 was significantly up-regulated in PC tissues compared to non-cancerous tissues. The analysis of correlation between the expression level of miR-153 and clinicopathological factors revealed a statistically significant correlation with the stage of the tumor process according to tumor, node, metastasis (TNM) staging system (p = 0.0256). ROC curve analysis was used to evaluate the predictive ability of miR-153 for metastasis development and it revealed miR-153 as a potential prognostic marker (AUC = 0.85; 95%CI 0.75–0.95; sensitivity = 0.72, specificity = 0.86)). According to logistic regression model the high expression of miR-153 increased the risk of metastasis development (odds ratios = 3.14, 95% CI 1.62–8.49; p-value = 0.006). Whole exome sequencing revealed nonsynonymous somatic mutations in collagen type IV alpha 1 (COL4A1), collagen type IV alpha 3 (COL4A3), forkhead box protein O1 (FOXO1), 2-hydroxyacyl-CoA lyase 1 (HACL1), hypoxia-inducible factor 1-alpha (HIF-1A), and nidogen 2 (NID2) genes. Moreover, KEGG analysis revealed that the extracellular matrix–receptor (ECM-receptor) interaction pathway is mainly involved in PC. Conclusion MiR-153 is up-regulated in PC tissues and may play an important role in aggressive PC by targeting potential target genes.
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Project description:Background and Objectives: Over decades, prostate cancer (PCa) has become one of the leading causes of cancer mortality in men. Extensive evidence exists that microRNAs (miRNAs or miRs) are key players in PCa and a new class of non-invasive cancer biomarkers. Materials and Methods: We performed miRNA profiling in plasma and tissues of PCa patients and attempted the validation of candidate individual miRs as biomarkers. Results: The comparison of tissue and plasma profiling results revealed five commonly dysregulated miRs, namely, miR-130a-3p, miR-145-5p, miR-148a-3p, miR-150-5p, and miR-365a-3p, of which only three show concordant changes-miR-130a-3p and miR-150-5p were downregulated and miR-148a-3p was upregulated in both tissue and plasma samples, respectively. MiR-150-5p was validated as significantly downregulated in both plasma and tissue cancer samples, with a fold change of -2.697 (p < 0.001), and -1.693 (p = 0.035), respectively. ROC analysis showed an area under the curve (AUC) of 0.817 (95% CI: 0.680-0.995) for plasma samples and 0.809 (95% CI: 0.616-1.001) for tissue samples. Conclusions: We provide data indicating that miR-150-5p plasma variations in PCa patients are associated with concordant changes in prostate cancer tissues; however, given the heterogeneous nature of previous findings of miR-150-5p expression in PCa cells, additional future studies of a larger sample size are warranted in order to confirm the biomarker potential and role of miRNA-150-5p in PCa biology.
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