Development and validation of novel inflammatory response-related gene signature to predict prostate cancer recurrence and response to immune checkpoint therapy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE210205 | GEO | 2022/08/04
REPOSITORIES: GEO
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Project description:Accurate estimation of recurrence risk is needed for optimal treatment of clinically localized prostate cancer (PCa) patients. We combined classical clinicopathological predictors of biochemical recurrence (BCR) and molecular markers into a new risk score for predicting BCR after radical prostatectomy (RP). A retrospective study which included 122 PCa patients who attended our department between 2000 and 2007 was conducted. Total RNA was isolated from formalin-fixed paraffin embedded PCa tissue. Gene expression patterns were analyzed in 21 selected samples from 7 localized, 6 locally advanced, and 8 metastatic PCa patients using Illumina microarrays. Expression levels of 41 genes were validated by quantitative PCR in an independent retrospective series of 101 patients with ≥ 10 years follow-up who underwent RP for clinically localized PCa. Univariate and multivariate logistic regression analysis were used to identify individual predictors of BCR. A risk score (RS) for predicting BCR including clinicopathological and gene expression data was developed and Kaplan-Meier curves were generated. Interaction networks between the genes of the model were built by GeneMANIA Cytoscape plugin. In a median follow-up of 120 months (range 3-190), 37 patients developed BCR (36.6%). Expression levels of 7,930 transcripts differed between clinically localized and locally advanced-metastatic PCa groups (FDR<0.1). A set of 41 genes were validated by quantitative PCR. Regression analysis showed that expression of ASF1B and MCL1 as well as Gleason score, extracapsular extension, seminal vesicle invasion and positive margins were independent prognostic factors of BCR. A RS generated using these gene expression and clinicopathological variables was able to discriminate between two groups of patients with a significantly different probability of BCR (HR 6.24; CI 3.23-12.4, p<0.01), improving the individual discriminative performance of each of these variables on their own. Direct interactions between the two genes of the model were not found. In conclusion, identification of new gene expression patterns associated with a high probability of BCR in clinically localized PCa patients treated with RP, and their combination with clinicopathological variables in a robust, easy-to-use and reliable classifier may contribute to improve PCa risk stratification and, consequently, to tailor treatment and surveillance strategies in these patients.
2024-04-23 | GSE149226 | GEO
Project description:Background The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change > 2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed to evaluate biochemical recurrence (BCR)-free survival. Results The identification of 150 DEGs between ERGhigh and ERGlow tumors revealed clustering of most of the non-BCR cases (60%) into de ERGhigh group and most of the BCR cases (60.8%) in ERGlow group. Kaplan-Meier survival curves showed a worst BCR-free survival for ERGlow patients, and a significant reduced risk of BCR was observed for ERGhigh cases (OR = 0.29 (95%CI, 0.10-0.8). Enrichment pathway analysis identified metabolic-related pathways, such as the renin-angiotensin system and angiotensin maturation system, the linoleic acid metabolism, and polyamines metabolism in these ERG groups. Conclusions ERGlow tumor cases were associated with poor BCR-free survival in our Hispanic/Latino patients, with metabolism-related pathways altered in the BCR progression. Impact Our findings suggest the need to dissect the role of diet, metabolism and lifestyle as risk factors for more aggressive PCa subtypes.
2022-10-27 | GSE216490 | GEO
Project description:The DNA methylation value in early-stage hepatocellular carcinoma was undetermined. The Illumina Infinium 450k Human DNA methylation Beadchip was used to identify recurrence-related abbrent CpG methylation. This study was performed in a total of 66 early-stage HCC samples, including 29 recurrence samples and 37 recurrence-free samples
2017-04-30 | E-GEOD-75041 | biostudies-arrayexpress
Project description:Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy which have low accuracy. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens following optimized sample preparation protocol and LC-MS/MS. Comparative analysis of 86 PCa samples among grade groups 1-5 identified 301 differentially expressed proteins involved in metabolism, angiogenesis, response to stress and cytoskeleton organization. Additional analysis based on biochemical recurrence (BCR; BCR+ n=14, BCR- n=51) revealed 197 differentially expressed proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins (NPM1, UQCRH, HSPA9, MRPL3, VCAN, SERBP1, HSPE1) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness and persistence. Notably, our observations for NPM1, UQCRH and VCAN were validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. UQCRH levels were also associated with 5-year survival. Our study provides valuable insights on the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.
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Project description:We developed a 33-gene signature that is strongly correlated to the time to recurrence in non-small cell lung cancer (NSCLC). The signature was validated retrospectively in 5 cohorts of 972 NSCLC patients and in one prospective study of 111 NSCLC Stage IA patients. In all cohorts, and all stages of the disease, the signature identified a rare, aggressive tumor type that had a high proportion of recurrence after surgery and a median survival of 35 months (95% C.I.: 19-58). This tumor type forms a separate cluster in an analysis of the expression of the 33 genes in patient tumors. The signature is associated with cellular processes required by rapidly growing and spreading tumors: cell migration and invasion, vascularization, and response to hypoxia. The signature also identifies patients with good prognosis (median survival 114 months, (95% C.I.: 85-160), and intermediate prognosis (median survival 61 months (95% C. I.: 50-73). The signature is quite robust and works on tumor samples archived in RNAlater, Tissue-Tek, or formalin-fixed and paraffin embedded. 156 samples -------------------------------- *** Submitter has not provided information such as time to recurrence. Thus, the data is incomplete.
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Project description:Comparison of circulating miRNA levels in patients who experienced rapid biochemical recurrence or no recurrence following radical prostatectomy
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Project description:Comparison of circulating miRNA levels in patients who experienced rapid biochemical recurrence or no recurrence following radical prostatectomy qRT-PCR miRNA expression profiling of patient serum
2013-05-22 | E-GEOD-47125 | biostudies-arrayexpress
Project description:The DNA methylation value in early-stage hepatocellular carcinoma was undetermined. The Illumina Infinium 450k Human DNA methylation Beadchip was used to identify recurrence-related abbrent CpG methylation.
2017-04-30 | GSE75041 | GEO
Project description:We developed a 33-gene signature that is strongly correlated to the time to recurrence in non-small cell lung cancer (NSCLC). The signature was validated retrospectively in 5 cohorts of 972 NSCLC patients and in one prospective study of 111 NSCLC Stage IA patients. In all cohorts, and all stages of the disease, the signature identified a rare, aggressive tumor type that had a high proportion of recurrence after surgery and a median survival of 35 months (95% C.I.: 19-58). This tumor type forms a separate cluster in an analysis of the expression of the 33 genes in patient tumors. The signature is associated with cellular processes required by rapidly growing and spreading tumors: cell migration and invasion, vascularization, and response to hypoxia. The signature also identifies patients with good prognosis (median survival 114 months, (95% C.I.: 85-160), and intermediate prognosis (median survival 61 months (95% C. I.: 50-73). The signature is quite robust and works on tumor samples archived in RNAlater, Tissue-Tek, or formalin-fixed and paraffin embedded.
2016-02-11 | GSE77803 | GEO
Project description:Though several approaches for improving therapy have been carried out, the prognoses of TSCC patients still remains poor. Furthermore, biological markers, which are able to distinguish patients at high risk of recurrence has not been sufficiently explored. In this study, we identified and validated the 30-specific genes for predicting TSCC patiens prognosis. In addition, the gene expression profiling data was successfully converted to protein expression profiling data.
2017-07-31 | GSE78060 | GEO