A Comparative in Silico Analysis of CD24's Prognostic Value in Human and Canine Prostate Cancer.
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ABSTRACT:
SUBMITTER: Leis-Filho AF
PROVIDER: S-EPMC8004660 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:N6-methyladenosine (m6A) is the most prevalent RNA modification. While the role of m6A in prostate cancer remains unknown. We aim to measure the effects of m6A methylation regulatory genes during the development and progression of prostate cancer. METHODS:We collected transcriptome information and gene-level alteration data from The Cancer Genome Atlas datasets. The log-rank test and Cox regression model were used to examine the prognosis value of m6A methylation regulatory genes of prostate cancer. RESULTS:We discovered that most of m6A methylation regulators were highly expressed in aggressive prostate cancer. Univariable and multivariable Cox regression results showed that the expression of Insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1) and N6-adenosine-methyltransferase non-catalytic subunit (METTL14) and copy number variant of AlkB Homolog 5 (ALKBH5) were considerably associated with a recurrence-free survival of prostate cancer. Furthermore, a high level of m6A methylation in mRNA promotes the progression of prostate cancer via regulating subcellular protein localization. CONCLUSION:Patients with a high level of mRNA methylation resulted from overexpression of reader proteins and methyltransferase complexes had poor survival benefits through influencing protein subcellular location in prostate cancer.
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Project description:Canine Mast cell tumors (MCTs) constitute approximately 21% of all canine skin tumors. Despite the use of comprehensive grading systems, biological aggressiveness is sometimes difficult to predict, therefore there is a need for better prognostic markers. Progression in various cancers involves DNA hypermethylation, hypomethylation and epigenetic enzyme dysregulation. Therefore, global levels of 5-methylcytosine, 5-hydroxymethylcytosine and associated enzymes DNMT1, and IDH1 expression may predict MCT aggressiveness. A tissue microarray (TMA) with cores from 244 different tumor samples from 189 dogs was immunolabelled and used to quantify the global DNA methylation and hydroxymethylation levels as well as the levels of the enzymes involved in DNA methylation and their relationship with canine MCT outcome. From the immunolabelled TMA, H-scores were generated using QuPath (v0.1.2) and analyzed with associated patient data. High 5MC and DNMT1, and low IDH1 levels were associated with poorer outcome when looking at all canine MCT cases. High 5MC levels showed significance for shorter disease-free interval (DFI) in subcutaneous cases and high 5MC levels showed poorer DFI and overall survival (OS) in cases with Kiupel's grading system high grade. Cases with grade II in Patnaik's grading system showed better DFI with low levels of DNMT1 and better OS with low levels of 5MC and 5HMC. High levels of DNMT1 staining were also associated with shorter DFI for dermal MCTs. For cases that received adjuvant therapy in addition to surgery, all parameters except IDH1 were significantly associated with OS. Therefore, there is potential for DNA methylation status and levels of enzymes associated with DNA methylation pathways to better predict outcome in canine MCT, and to possibly influence treatment decisions.
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Project description:Canine and human bladder cancer present similar anatomical, morphological, and molecular characteristics, and dogs can be considered a model for human bladder cancer. However, the veterinary literature lacks information regarding cross-validation analysis between human and canine large-scale data. Therefore, this research aimed to perform a meta-analysis of the canine literature on bladder cancer, identifying genes and proteins previously evaluated in these studies. In addition, we also performed a cross-validation of the canine transcriptome data and the human data from The Cancer Genome Atlas (TCGA) to identify potential markers for both species. The meta-analysis was performed using the following indexing terms: "bladder" AND "carcinoma" AND "dog" in different international databases, and 385 manuscripts were identified in our initial search. Then, several inclusion criteria were applied, and only 25 studies met these criteria. Among these studies, five presented transcriptome data, and 20 evaluated only isolated genes or proteins. Regarding the studies involving isolated protein analysis, the HER-2 protein was the most studied (3/20), followed by TAG-72 (2/20), COX-2 (2/20), survivin (2/20), and CK7 (2/20), and the remaining nine studies evaluated one isolated protein each. Regarding the cross-validation analysis of human and canine transcriptome data, we identified 35 dysregulated genes, including ERBB2, TP53, EGFR, and E2F2. Our results demonstrate that the canine literature on bladder cancer previously focused on the evaluation of isolated markers with no association with patient survival. This limitation may be related to the lack of a homogenous protocol for treating patients and the lack of follow-up during treatment. In addition, the lack of information regarding tumor muscle invasion can be considered an important limitation when comparing human and canine bladder tumors. Our in silico analysis involving canine and human transcriptome data provided several genes with the potential to be markers for both human and canine bladder tumors, and these genes should be considered for future studies on canine bladder cancer.
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Project description:Cluster of differentiation (CD) antigens are cell surface markers used to differentiate haematopoietic cell types. These antigens are present in various malignancies and are reportedly linked to patient prognosis; however, they have not been implemented as prostate cancer progression markers. Here, we aimed to assess the impact of genetic variation in haematopoietic cell CD markers on clinical outcomes in patients with prostate cancer. An association study of 458 patients with prostate cancer was conducted to identify single-nucleotide polymorphisms in 11 candidate CD marker genes associated with biochemical recurrence (BCR) after radical prostatectomy. Identified predictors were further evaluated in an additional cohort of 185 patients. Joint population analyses showed that CD1B rs3181082 is associated with BCR (adjusted hazard ratio 1.42, 95% confidence interval 1.09-1.85, p = 0.010). In addition, rs3181082 overlapped with predicted transcriptional regulatory elements and affected CD1B expression. Furthermore, low CD1B expression correlated with poorer BCR-free survival. Our results indicated that CD1B rs3181082 confers prostate cancer progression and may help improve clinical prognostic stratification.
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Project description:Metastatic prostate cancer (mPC) has a poor prognosis, and new treatment strategies are currently being offered for patients in clinical practice, but mPC is still incurable. A considerable proportion of patients with mPC harbor homologous recombination repair (HRR) mutations, which may be more sensitive to poly (ADP-ribose) polymerase inhibitors (PARPis). We retrospectively included genomic and clinical data from 147 patients with mPC from a single clinical center, with a total of 102 circulating tumor DNA (ctDNA) samples and 60 tissue samples. The frequency of genomic mutations was analyzed and compared with that in Western cohorts. Cox analysis was used to assess progression-free survival (PFS) and prognostic factors related to prostate-specific antigen (PSA) after standard systemic therapy for mPC. The most frequently mutated gene in the HRR pathway was CDK12 (18.3%), followed by ATM (13.7%) and BRCA2 (13.0%). The remaining common ones were TP53 (31.3%), PTEN (12.2%), and PIK3CA (11.5%). The frequency of BRCA2 mutation was close to that of the SU2C-PCF cohort (13.3%), but the frequency of CDK12, ATM, and PIK3CA mutations was significantly higher than that in the SU2C-PCF cohort: 4.7%, 7.3%, and 5.3%, respectively. CDK12 mutation were less responsive to androgen receptor signaling inhibitors (ARSIs), docetaxel, and PARPi. BRCA2 mutation helps predict PARPi efficacy. Additionally, androgen receptor (AR)-amplified patients do not respond well to ARSIs, and PTEN mutation are associated with poorer docetaxel response. These findings support the genetic profiling of patients with mPC after diagnosis to guide treatment stratification to customize personalized treatment.
| S-EPMC9988500 | biostudies-literature
Project description:Elevated levels of miR-21 expression are associated with many cancers, suggesting it may be a promising clinical biomarker. In prostate cancer (PCa), however, there is still no consensus about the usefulness of miR-21 as an indicator of disease progression. This systematic review and meta-analysis was conducted to investigate the value of miR-21 expression as a prognostic measurement in PCa patients. Medline (Ovid), EMBASE, Web of Science, Scopus and Cochrane Library databases were systematically searched for relevant publications between 2010 to 2021. Studies exploring the relationship between miR-21 expression, PCa prognosis and clinicopathological factors were selected for review. Those reporting hazard ratio (HR) and 95% confidence intervals (CIs) were subject to meta-analyses. Fixed-effect models were employed to calculated pooled HRs and 95% CIs. Risk of bias in each study was assessed using QUIPS tool. Certainty of evidence in each meta-analysis was assessed using GRADE guidelines. A total of 64 studies were included in the systematic review. Of these, 11 were eligible for inclusion in meta-analysis. Meta-analyses revealed that high miR-21 expression was associated with poor prognosis: HR = 1.58 (95% CI = 1.19-2.09) for biochemical recurrence, MODERATE certainty; HR = 1.46 (95% CI = 1.06-2.01) for death, VERY LOW certainty; and HR = 1.26 (95% CI = 0.70-2.27) for disease progression, VERY LOW certainty. Qualitative summary revealed elevated miR-21 expression was significantly positively associated with PCa stage, Gleason score and risk groups. This systematic review and meta-analysis suggests that elevated levels of miR-21 are associated with poor prognosis in PCa patients. miR-21 expression may therefore be a useful prognostic biomarker in this disease.
| S-EPMC8753345 | biostudies-literature
Project description:BackgroundAccurate and non-invasive diagnostic and prognostic markers are necessary to improve patient outcomes. MicroRNAs have been proposed as relatively non-invasive and pertinent biomarkers. miR-93 has been studied for its potential as a diagnostic and prognostic marker in prostate cancer (PCa), but findings from individual studies are inconsistent. We conducted a meta-analysis of its overall differential expression in 13 PCa studies and a bioinformatics analysis to provide a comprehensive appraisal of its diagnostic and prognostic role.MethodsWe searched all published papers on miR-93 expression in PCa up to Nov 30, 2022 using PubMed, Science Direct, Web of Science, Cochrane Central Register of Controlled Trials databases. We used RevMan software to Meta-analyze the included literature. A bioinformatics analysis of genes and pathways that might be target to the effect of the mature miR-93-5p was carried out.ResultsThe pooled standardized mean difference (SMD) of miR-93 expression in PCa, its area under the curve (AUC) and hazard ratio (HR) were 1.26, 95% CI [-0.34-2.86], 0.84, 95% CI [0.76 -0.93] and 1.67, 95% CI [0.98, 2.84] respectively. Bioinformatics analysis revealed that mature miR-93-5p may regulate genes such as SMAD1, SMAD7 and MAPK and the PI3K-Akt signaling pathways.ConclusionmiR-93 has significant diagnostic and prognostic value in PCa. These findings highlight the potential of miR-93 as a non-invasive biomarker for PCa and may contribute to earlier detection and prognostic assessment. The target genes and signaling pathways regulated by miR-93 may provide insights into the underlying molecular mechanisms of PCa.
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Project description:Background: FAS is a classical death receptor involved in the FAS/FAS ligand (FASL) apoptosis pathway and plays a role in anti-tumor activity. Some studies have recently reported that FAS can serve as an oncogene that promotes tumor proliferation and maintains the stemness of tumor cells. Hence, its prognostic value in malignancies remains controversial. Methods: we assessed the prognostic value of FAS mRNA in several types of tumors by online platforms including Kaplan-Meier Plotter and SurvExpress. Results: FAS mRNA was associated with better overall survival (OS) in breast cancer (Hazard ratio (HR): 0.59 [0.47, 0.73]; p=1.5e-06), gastric cancer (HR: 0.65 [0.54, 0.77]; p=8e-07) and non-small-cell lung cancer (NSCLC) (HR: 0.78 [0.69, 0.89]; p=0.00016), especially in lung adenocarcinoma (HR: 0.64 [0.51, 0.81], p=1.7e-04), female lung cancer (HR:0.72 [0.57, 0.9], p=0.0049) and patients who have never smoked (HR: 0.39 [0.21, 0.7], p=0.0012). However, a high level of FAS mRNA expression indicated poorer OS in pancreatic cancer (HR: 1.33 [1.06, 1.66]; p=0.01) and acute myeloid leukemia (AML) (HR: 1.57 [1.02, 2.41], p=0.04). Additionally, FAS showed no prognostic value in renal carcinoma, head and neck carcinoma, hepatic cancer, ovarian cancer, colorectal cancer or glioblastoma. The results from the Cell Miner tool revealed that FAS expression was associated with the sensitivity of tumor cells to cabozantinib and erlotinib. Conclusions: In summary, the dominant function of FAS may vary in different malignancies. FAS mRNA expression was correlated with better OS in breast cancer, gastric cancer and lung cancer, but worse OS in pancreatic cancer and AML. We also suggested that FAS mRNA expression could be a potential biomarker for cabozantinib and erlotinib.
| S-EPMC6959050 | biostudies-literature
Project description:To screen target gene cluster by bioinformatics analysis and verify them by in vitro experiment and clinicopathological correlation analysis. We try to find a new biomarker with prognostic value for prostate cancer (PCa). 42 candidate marker genes were constructed by protein protein interaction (PPI) network and enriched by KEGG pathway to find out the gene cluster we are interested in. Prognostic model was established to preliminarily analyze the prognostic value of this gene cluster in PCa, and Cox risk regression was used for comparative analysis. Immunohistochemistry was used to detect the expression of each gene in clinical tissue microarray. Finally, we analyzed the correlation between each gene and their clinicopathological features of PCa combined with TCGA clinical data. Based on the analysis of PPI and KEGG, we found the target gene cluster (FCGR3A, HAVCR2, CCR7 and CD28). Prognostic model analysis showed that this gene cluster had the ability to predict biochemical recurrence, and the survival rate and ROC analysis showed favorable prediction effect. Univariate Cox regression analysis showed that the risk scores of Gleason score (GS), T stage, N stage and PSA were significantly different (P<0.05), and the risk ratio of high expression was 2.30 times that of low expression (P=0.004). However, it was not statistically significant in multivariate Cox regression analysis (P>0.05). The results of tissue microarray showed that FCGR3A and HAVCR2 were highly expressed in PCa (P<0.01), while the expression of CCR7 and CD28 had no significant difference (P>0.05). Kaplan-Meier analysis showed that there was significant difference in BCR free survival of FCGR3A and HAVCR2 (FCGR3A, P=0.010; HAVCR2, P=0.018), while the expression of CCR7 and CD28 had no significant difference on the survival and prognosis of PCa patients (P>0.05). TCGA clinical data analysis found that the expression of FCGR3A had a unique correlation with the clinicopathological features of PCa, which was closely related to the tumor stage. The expression of FCGR3A is related to BCR free survival of PCa patients. Therefore, FCGR3A is a new biomarker with potential prognostic value of PCa.
| S-EPMC9730230 | biostudies-literature
Project description:BackgroundThe tumor microenvironment (TME) has recently been proven to play a crucial role in the development and prognosis of tumors. However, the current knowledge on the potential of the TME in prostate cancer (PCa) remains scarce.PurposeThis study aims to elucidate the value of TME-related genes for PCa prognosis by integrative bioinformatics analysis.Materials and methodsWe downloaded the immune and stromal scores of PCa samples via the ESTIMATE and correlated these scores to clinicopathological characteristics and recurrence-free survival (RFS) of patients. Based on these scores, the TME-related differentially expressed genes were identified for functional enrichment analysis. Cox regression analyses were performed to identify prognostic genes and establish a predictive risk model. Moreover, gene set enrichment analysis (GSEA) was performed to evaluate the relationship between risk score and immune pathway.ResultsThe stromal and immune scores were associated with clinicopathological characteristics and RFS in PCa patients. In total, 238 intersecting differentially expressed genes were identified. Functional enrichment analysis further revealed that these genes dramatically participated in the immune-related pathways. The immune-related risk model was built with C-type lectin domain containing 7A (CLEC7A) and collagen type XI alpha 1 chain (COL11A1) using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of CLEC7A and COL11A1 were significantly associated with the RFS. Further, the RFS time in high-risk group was significantly shorter than that in low-risk group. The areas under the curve for the risk model in predicting 3- and 5-year RFS rates were 0.694 and 0.731, respectively. GSEA suggested that immunosuppression existed in high-risk PCa patients.ConclusionCLEC7A and COL11A1 were selected to build a predictive risk model, which may help clinicians to assess the prognosis of PCa patients and select appropriate targets for immunotherapy.
| S-EPMC8254424 | biostudies-literature