Prognostic significance of lncRNA AP004608.1 in prostate cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Li W
PROVIDER: S-EPMC9556701 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Prognostic significance of lncRNA AP004608.1 in prostate cancer.
Li Wei W Zhou Runze R Sun Bo B Jin Xin X Chen Yuan Y Xu Xuefen X
Frontiers in oncology 20220929
This study aimed to screen and determine the value of AP004608.1 expression as a biomarker for Prostate cancer (PCa) survival. We investigated the expression and prognosis of AP004608.1 through bioinformatics analysis. Low AP004608.1 expression predicted favorable Overall survival (OS) and Progression-free survival (PFS) in PCa patients, according to the Cancer Genome Atlas (TCGA) database. Cox regression demonstrated that low AP004608.1 expression were in-dependent biomarkers for OS. Moreover, ...[more]
Similar Datasets
Project description:BACKGROUND: Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC. METHODS: Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays representing 267 radical prostatectomy (RP) and 111 conservatively treated (CT) PC patients. Clinical end points were recurrence-free survival (RFS) and cancer-specific survival (CSS), respectively. The ANPEP promoter methylation levels were determined by bisulphite sequencing or MethyLight analysis in 278 nonmalignant and PC tissue samples, and in cell lines. RESULTS: The APN expression was significantly downregulated in PC compared with nonmalignant prostate tissue samples. Aberrant promoter hypermethylation was frequently observed in PC tissue samples, and 5-aza-2'-deoxycytidine induced ANPEP expression in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis marker (vascular endothelial growth factor or microvessel density) improved risk prediction significantly in both cohorts. CONCLUSION: Our results suggest negative APN immunoreactivity as a new independent adverse prognostic factor for patients with clinically localised PC and, furthermore, that epigenetic mechanisms are involved in silencing of ANPEP in PC.
| S-EPMC3566819 | biostudies-other
Project description:Based on the importance of basement membrane (BM) in cancer invasion and metastasis, we constructed a BM-associated lncRNA risk model to group bladder cancer (BCa) patients. Transcriptional and clinical data of BCa patients were downloaded from The Cancer Genome Atlas (TCGA), and the expressed genes of BM-related proteins were obtained from the BM-BASE database. We download the GSE133624 chip data from the GEO database as an external validation dataset. We screened for statistically different BM genes between tumors and adjacent normal tissues. Co-expression analysis of lncRNAs and differentially expressed BM genes was performed to identify BM-related lncRNAs. Then, differentially expressed BM-related lncRNAs (DEBMlncRNAs) between tumor and normal tissues were identified. Univariate/multivariate Cox regression analysis was performed to select lncRNAs for risk assessment. LASSO analysis was performed to build a prognostic model. We constructed a model containing 8 DEBMlncRNAs (AC004034.1, AL662797.1, NR2F1-AS1, SETBP1-DT, AC011503.2, AC093010.2, LINC00649 and LINC02321). The prognostic risk model accurately predicted the prognosis of BCa patients and revealed that tumor aggressiveness and distant metastasis were associated with higher risk scores. In this model, we constructed a nomogram to assist clinical decision-making based on clinicopathological characteristics such as age, T, and N. The model also showed good predictive power for the tumor microenvironment and mutational burden. We validated the expression of eight lncRNAs using the dataset GSE133624 and two human bladder cancer cell lines (5637, BIU-87) and examined the expression and cellular localization of LINC00649 and AC011503.2 using a human bladder cancer tissue chip. We found that knockdown of LINC00649 expression in 5637 cells promoted the proliferation of 5637 cells.Our eight DEBMlncRNA risk models provide new insights into predicting prognosis, tumor invasion, and metastasis in BCa patients.
| S-EPMC9590283 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a common disease of the digestive system with no curative treatments. Long noncoding RNA tyrosine protein kinase transmembrane receptor 1 antisense RNA 1 (lncRNA ROR1‑AS1) is an lncRNA whose functions have been predicted in human diseases; however, its important role in cancer has been probed only in mantle cell lymphoma, not in HCC. Therefore, the present study aimed to elucidate the prognostic significance of lncRNA ROR1‑AS1 in HCC. The Cancer Genome Atlas Liver Hepatocellular Carcinoma was used to analyze the expression of ROR1‑AS1 in liver cancer. χ2 tests were performed to evaluate associations between clinical characteristics and ROR1‑AS1 expression. The role of ROR1‑AS1 in HCC prognosis was assessed using Kaplan‑Meier curves and proportional hazards model (Cox) analysis. Gene set enrichment analysis was performed by using a Gene Expression Omnibus dataset. At the same time, Multi Experiment Matrix was used to predict genes that may be co‑expressed with ROR1‑AS1. The Database for Annotation, Visualization and Integrated Discovery and KO‑Based Annotation System were used to analyze the most closely associated cytological behaviors and pathways in HCC. Then, the genes in the three databases were integrated to screen mRNAs, microRNAs and lncRNAs that had co‑expression relationships with ROR1‑AS1. Cytoscape, Search Tool for the Retrieval of Interacting Genes/Proteins and Molecular Evolutionary Genetics Analysis were used to map potential regulatory networks and developmental relationships associated with ROR1‑AS1. Finally, 12 genes most closely associated with ROR1‑AS1 were identified, and their relationship was described using a Circos plot. The results showed that ROR1‑AS1 was upregulated in HCC, and its expression was related to clinical stage, T stage and N stage. Furthermore, Kaplan‑Meier curves and Cox analysis indicated that high expression of ROR1‑AS1 was associated with poor prognosis, and that ROR1‑AS1 was an independent risk factor for HCC. Co‑expression data suggested that there may be a large regulatory network of 45 genes with indirect associations with ROR1‑AS1, a small regulatory network of 15 genes with direct or indirect regulatory relationships, and a special regulatory network containing 12 genes directly associated with ROR1‑AS1. The present findings indicated that high expression of ROR1‑AS1 suggests poor prognosis in patients with HCC.
| S-EPMC6908930 | biostudies-literature
Project description:Hepatocellular carcinoma (HCC) is a common digestive system disease with no curative treatment. Zinc finger protein 385D antisense RNA 2 (ZNF385D‑AS2) is a long non‑coding RNA (lncRNA) that has been predicted to function in human diseases, including several types of cancer. Yet, it has not been investigated in relation to liver cancer. Thus, the present study was designed with an aim to elucidate the prognostic significance of lncRNA ZNF385D‑AS2 in HCC. The Cancer Genome Atlas‑Liver Hepatocellular Carcinoma (TCGA‑LIHC) collection of data was utilized to analyze the expression of lncRNA ZNF385D‑AS2 in liver cancer. Then Chi‑square tests were used to evaluate the correlation between clinical characteristics and lncRNA ZNF385D‑AS2 expression. The significance of lncRNA ZNF385D‑AS2 in patient prognosis was evaluated using Kaplan‑Meier curves and Cox analysis. Concomitantly, Gene Set Enrichment Analysis (GSEA) was performed to analyze the most closely related cytological behavior. Finally, we used the Database for Annotation, Visualization and Integrated Discovery (DAVID) and KOBAS software and data from the Gene Expression Omnibus (GEO) database to analyze the possible competing endogenous RNA (ceRNA) network pattern as well as the co‑expression network in liver cancer. Based on the results, analysis of RNA‑Seq gene expression data for 303 patients with primary tumors revealed low expression of ZNF385D‑AS2 in liver cancer. Low expression of ZNF385D‑AS2 was found to be significantly associated with sex (P=0.050), T stage (P=0.049), M stage (P=0.040), N stage (P<0.001) and clinical stage (P=0.037). Patients with ZNF385D‑AS2 low‑expression liver cancers had a shorter median overall survival compared with the patients with ZNF385D‑AS2 high‑expression liver cancers (P=0.0079). Cox analysis identified ZNF385D‑AS2 low‑expression as an independent prognostic variable (AUC=0.594) for overall survival in liver cancer patients. Co‑expression and ceRNA predictive analysis data suggested that there may be a regulatory signaling axis between ZNF385D‑AS2 and miR‑96 and miR‑182. In conclusion, our results suggests that low expression of ZNF385D‑AS2 is predictive of a poor prognosis of liver cancer patients.
| S-EPMC6667919 | biostudies-literature
Project description:We have recently shown that centrosomal protein 57 (CEP57) is overexpressed in a subset of human prostate cancers. CEP57 is involved in intracellular transport processes, and its overexpression causes mitotic defects as well as abnormal microtubule nucleation and bundling. In the present study, we further characterized the prognostic and functional role of CEP57 in prostate cancer. Unexpectedly, we found that high CEP57 expression is an independent prognostic factor for a more favorable biochemical recurrence-free survival in two large patient cohorts. To reconcile this finding with the ability of CEP57 to cause cell division errors and thus potentially promote malignant progression, we hypothesized that alterations of microtubule-associated transport processes, in particular nuclear translocation of the androgen receptor (AR), may play a role in our finding. However, CEP57 overexpression and microtubule bundling had, surprisingly, no effect on the nuclear translocation of the AR. Instead, we found a significant increase of cells with disarranged microtubules and a cellular morphology suggestive of a cytokinesis defect. Because mitotic dysfunction leads to a reduced daughter cell formation, it can explain the survival benefit of patients with increased CEP57 expression. In contrast, we show that a reduced expression of CEP57 is associated with malignant growth and metastasis. Taken together, our findings underscore that high CEP57 expression is associated with mitotic impairment and less aggressive tumor behavior. Because the CEP57-induced microtubule stabilization had no detectable effect on AR nuclear translocation, our results furthermore suggest that microtubule-targeting therapeutics used in advanced prostate cancer such as docetaxel may have modes of action that are at least in part independent of AR transport inhibition.
| S-EPMC4700294 | biostudies-literature
Project description:Bladder cancer (BLCA) is one of the most common urological cancer with increasing cases and deaths every year. In the present study, we aim to construct an immune-related prognostic lncRNA signature (IRPLS) in bladder cancer (BLCA) patients and explore its immunogenomic implications in pan-cancers. First, the immune-related differentially expressed lncRNAs (IRDELs) were identified by 'limma' R package and the score of IRPLS in every patient were evaluated by Cox regression. The dysregulation of IRDELs expression between cancer and para-cancer normal tissues was validated through RT-qPCR. Then, we further explore the biological functions of a novel lncRNA from IRPLS, RP11-89 in BLCA using CCK8 assay, Transwell assay and Apoptosis analysis, which indicated that RP11-89 was able to promote cell proliferation and invasive capacity while inhibits cell apoptosis in BLCA. In addition, we performed bioinformatic methods and RIP to investigate and validate the RP11-89/miR-27a-3p/PPARγ pathway in order to explore the mechanism. Next, CIBERSORT and ESTIMATE algorithm were used to evaluate abundance of tumour-infiltrating immune cells and scores of tumour environment elements in BLCA with different level of IRPLS risk scores. Finally, multiple bioinformatic methods were performed to show us the immune landscape of these four lncRNAs for pan-cancers. In conclusion, this study first constructed an immune-related prognostic lncRNA signature, which consists of RP11-89, PSORS1C3, LINC02672 and MIR100HG and might shed lights on novel targets for individualized immunotherapy for BLCA patients.
| S-EPMC8093983 | biostudies-literature
Project description:Recently, we have shown that HLA-A*02:01 and HLA-A*24:02 in de novo metastatic prostate cancer (MPCa) have an important role in disease progression. Since de novo MPCa represents a small group among patients diagnosed with prostate cancer (PCa), it was obvious to try to extend the validity of our results to larger cohorts of PCa patients. Herein, we analyzed patients irrespective of their disease status at diagnosis to include, besides patients with MPCa, those with localized PCa (LPCa). Our goal was to specify the prognostic value of HLA-A*02:01 and HLA-A*24:02 for overall survival (OS) prospectively and for early biochemical recurrence (BCR) and castrate resistance (CR) as additional clinical endpoints in a prospective/retrospective manner, to improve clinical decisions for patients covering all stages of PCa. On univariate analysis, HLA-A alleles were significantly associated as prognostic biomarkers with early BCR (p = 0.028; HR = 1.822), OS (p = 0.013; HR = 1.547) and showed a trend for CR (p = 0.150; HR = 1.239). On multivariate analysis, HLA-A alleles proved to be independent prognosticators for early BCR (p = 0.017; HR = 2.008), CR (p = 0.005; HR = 1.615), and OS (p = 0.002; HR = 2.063). Kaplan-Meier analyses revealed that patients belonging to the HLA-A*02:01+HLA-A*24:02- group progressed much faster to BCR and CR and had also shorter OS compared to HLA-A*24:02+ patients. Patients being HLA-A*02:01-HLA-A*24:02- exhibited varying clinical outcomes, pointing to the presence of additional HLA-A alleles with potential prognostic value. Our data underline the HLA-A alleles as valuable prognostic biomarkers for PCa that may assist with the appropriate treatment and follow-up schedule based on the risk for disease progression to avoid over-diagnosis and over-treatment.
| S-EPMC10572221 | biostudies-literature
Project description:Background: Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. Methods: A series of statistical analyses were used to identify the key CRLs that are closely related to the prognosis, and a prognostic CRlncSig was constructed. The predictive accuracy of the CRlncSig was further validated in an independent Gene Expression Omnibus (GEO) set. Then, we compared the immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor mutational burden (TMB), drug sensitivity, and efficacy of immunotherapy between the two subgroups. We further built a nomogram integrating the CRlncSig and different clinical traits to enhance the clinical application of the CRlncSig. Results: Nine hub CRLs, namely RGMB-AS1, TYMSOS, DANCR, LINC00702, LINC00240, LINC00996, DNM1P35, LINC00892, and TMEM254-AS1, were correlated with the overall survival (OS) of OC and a prognostic CRlncSig was established. The CRlncSig classified OC patients into two risk groups with strikingly different survival probabilities. The time-dependent ROC (tdROC) curves demonstrated good predictive ability in both the training cohort and an independent validation cohort. Multivariate analysis confirmed the independent predictive performance of the CRlncSig. We constructed a nomogram based on the CRlncSig, which can predict the prognosis of OC patients. The high-risk score was characterized by decreased immune cell infiltration and activation of stroma, while activation of immunity was observed in the low-risk subgroup. Moreover, patients in low-risk subgroups had more Immunophenoscore (IPS) and fewer immune escapes compared to high-risk subgroups. Finally, an immunotherapeutic cohort confirmed the value of the CRlncSig in predicting immunotherapy outcomes. Conclusions: The developed CRlncSig may be promising for the clinical prediction of OC patient outcomes and immunotherapeutic responses.
| S-EPMC11592286 | biostudies-literature
Project description:Prostate cancer (PCa) is a common and serious health issue among older men globally. Metabolic reprogramming, particularly involving lactate and mitochondria, plays a key role in PCa progression, but studies linking these factors to prognosis are limited. To identify novel prognostic markers of PCa based on lactate-mitochondria-related genes (LMRGs), RNA sequencing data and clinical information of PCa from The Cancer Genome Atlas (TCGA) and the cBioPortal database were used to construct a lactate-mitochondria-related risk signature. Here, we established a novel nine-LMRG risk signature for PCa, and Kaplan-Meier curves confirmed a worse prognosis for high-risk subgroups in the TCGA dataset. Meanwhile, a nomogram that effectively predicts the prognosis of PCa patients was also constructed. Next, close associations between the lactate-mitochondria-related signature and the immune microenvironment were examined to clarify the role of LMRGs in shaping the immune landscape. Furthermore, as the only lactate-related gene among the nine key prognostic risk genes, myeloperoxidase (MPO) was identified as a key factor that mediates lactate production in vitro and in vivo through attenuation of the glycolytic pathway. More importantly, MPO significantly inhibited PCa cell migration, invasion, and epithelial-mesenchymal transition (EMT), indicating its potential as an anticancer gene. Additionally, PCa with high MPO expression is highly sensitive to chemotherapeutic agents and mitochondrial inhibitors, highlighting its potential as an improved therapeutic strategy for PCa management.
| S-EPMC11743670 | biostudies-literature
Project description:Chromosome 8q gain is associated with poor clinical outcomes in prostate cancer, but the underlying biological mechanisms remain to be clarified. CSN5, a putative androgen receptor (AR) partner that is located on chromosome 8q, is the key subunit of the COP9 signalosome, which deactivates ubiquitin ligases. Deregulation of CSN5 could affect diverse cellular functions that contribute to tumor development, but there has been no comprehensive study of its function in prostate cancer. The clinical significance of CSN5 amplification/overexpression was evaluated in 16 prostate cancer clinical cohorts. Its oncogenic activity was assessed by genetic and pharmacologic perturbations of CSN5 activity in prostate cancer cell lines. The molecular mechanisms of CSN5 function were assessed, as was the efficacy of the CSN5 inhibitor CSN5i-3 in vitro and in vivo. Finally, the transcription cofactor activity of CSN5 in prostate cancer cells was determined. The prognostic significance of CSN5 amplification and overexpression in prostate cancer was independent of MYC amplification. Inhibition of CSN5 inhibited its oncogenic function by targeting AR signaling, DNA repair, multiple oncogenic pathways, and spliceosome regulation. Furthermore, inhibition of CSN5 repressed metabolic pathways, including oxidative phosphorylation and glycolysis in AR-negative prostate cancer cells. Targeting CSN5 with CSN5i-3 showed potent antitumor activity in vitro and in vivo. Importantly, CSN5i-3 synergizes with PARP inhibitors to inhibit prostate cancer cell growth. CSN5 functions as a transcription cofactor to cooperate with multiple transcription factors in prostate cancer. Inhibiting CSN5 strongly attenuates prostate cancer progression and could enhance PARP inhibition efficacy in the treatment of prostate cancer.
| S-EPMC9359627 | biostudies-literature