CAD/POLD2 gene expression is associated with poor overall survival and chemoresistance in bladder urothelial carcinoma

Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.

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Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer

Journal of Clinical Pathology ◽

10.1136/jclinpath-2017-204976 ◽

2018 ◽

Vol 71 (9) ◽

pp. 787-794 ◽

Cited By ~ 11

Author(s):

Stephanie Robertson ◽

Gustav Stålhammar ◽

Eva Darai-Ramqvist ◽

Mattias Rantalainen ◽

Nicholas P Tobin ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Overall Survival ◽

Survival Data ◽

Prognostic Value ◽

Molecular Subtype ◽

Axillary Lymph Node Metastasis ◽

Axillary Lymph ◽

Poor Overall Survival ◽

Breast Tumours

AimsThe accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome.MethodsTwo retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated.ResultsIn both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis.ConclusionsThis study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes.

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Gene Expression Signature in Urine for Diagnosing and Assessing Aggressiveness of Bladder Urothelial Carcinoma

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-09-3373 ◽

2010 ◽

Vol 16 (9) ◽

pp. 2624-2633 ◽

Cited By ~ 45

Author(s):

Lourdes Mengual ◽

Moisès Burset ◽

María José Ribal ◽

Elisabet Ars ◽

Mercedes Marín-Aguilera ◽

...

Keyword(s):

Gene Expression ◽

Urothelial Carcinoma ◽

Gene Expression Signature ◽

Expression Signature ◽

Bladder Urothelial Carcinoma

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The effect of tumor location on overall survival for pT2-4 bladder and upper tract urothelial carcinoma following radical surgery

Canadian Urological Association Journal ◽

10.5489/cuaj.6698 ◽

2020 ◽

Vol 15 (5) ◽

Author(s):

Andrew W. Tam ◽

Christine Liaw ◽

Eric Li ◽

Andrew B. Katims ◽

Rollin K. Say ◽

...

Keyword(s):

Overall Survival ◽

Urothelial Carcinoma ◽

Renal Pelvis ◽

Cox Regression ◽

Tumor Location ◽

Upper Tract Urothelial Carcinoma ◽

Upper Tract ◽

Risk Of Mortality ◽

Bladder Urothelial Carcinoma ◽

Definitive Surgery

Introduction: Historically, staging and treatment for upper tract urothelial carcinoma were extrapolated from bladder urothelial carcinoma literature. However, embryological, genetic, and anatomical differences exist between them. We sought to explore the relationship between location of urothelial cancer and overall survival (OS). Methods: Data was culled from the National Cancer Database from 2004–2015. Patients with pT2-pT4 treated with definitive surgery were included; those with metastatic disease or who received neoadjuvant or adjuvant treatment were excluded. Patients were stratified by tumor location and pathological stage. The primary outcome was OS. Secondary outcomes were predictors of mortality in each pT stage stratum. Results: A total of 11 330 patients with bladder, 954 patients with ureteral, and 1943 patients with renal pelvis urothelial carcinoma were analyzed. Mean followup was 43.3, 39.4, and 41.4 months for bladder, ureteral, and renal pelvis, respectively. On univariable analysis, ureteral pT2 was associated with worse OS compared to both bladder (61.3 vs. 80.4 months, p=0.007) and renal pelvis (61.3 vs. 80.5 months, p=0.014). Renal pelvis pT3 was associated with improved OS compared to both bladder (42.5 vs. 28.6 months, p=0.003) and ureteral (42.5 vs. 25.7 months, p<0.001). Renal pelvis pT4 had decreased survival compared to bladder (11.4 vs. 17.7 months, p<0.001). On multivariable Cox regression, only renal pelvis pT3 was associated with a 20% decreased risk of mortality compared to bladder pT3 (hazard ratio 0.80, 95% confidence interval 0.72–0.88, p<0.001). Conclusions: Renal pelvis pT3 is associated with lower mortality. Mutational and embryological differences may play a role in this disparity.

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Mining TCGA database for gene expression in ovarian serous cystadenocarcinoma microenvironment

PeerJ ◽

10.7717/peerj.11375 ◽

2021 ◽

Vol 9 ◽

pp. e11375

Author(s):

Youzheng Xu ◽

Yixin Xu ◽

Chun Wang ◽

Baoguo Xia ◽

Qingling Mu ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Strong Predictor ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Poor Overall Survival ◽

Protein Protein Interaction ◽

Serous Cystadenocarcinoma ◽

Kaplan Meier ◽

Limma Package

Background Ovarian cancer is one of the leading causes of female deaths worldwide. Ovarian serous cystadenocarcinoma occupies about 90% of it. Effective and accurate biomarkers for diagnosis, outcome prediction and personalized treatment are needed urgently Methods Gene expression profile for OSC patients was obtained from the TCGA database. The ESTIMATE algorithm was used to calculate immune scores and stromal scores of expression data of ovarian serous cystadenocarcinoma samples. Survival results between high and low groups of immune and stromal score were compared and differentially expressed genes (DEGs) were screened out by limma package. The Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and the protein-protein interaction (PPI) network analysis were performed with the g:Profiler database, the Cytoscape and Search Tool for the Retrieval of Interacting Genes (STRING-DB). Survival results between high and low immune and stromal score groups were compared. Kaplan-Meier plots based on TCGA follow up information were generated to evaluate patients’ overall survival. Results Eighty-six upregulated DEGs and one downregulated DEG were identified. Three modules, which included 49 nodes were chosen as important networks. Seven DEGs (VSIG4, TGFBI, DCN, F13A1, ALOX5AP, GPX3, SFRP4) were considered to be correlated with poor overall survival. Conclusion Seven DEGs (VSIG4, TGFBI, DCN, F13A1, ALOX5AP, GPX3, SFRP4) were correlated with poor overall survival in our study. This new set of genes can become strong predictor of survival, individually or combined. Further investigation of these genes is needed to validate the conclusion to provide novel understanding of tumor microenvironment with ovarian serous cystadenocarcinoma prognosis and treatment.

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CDK13 Mutations Drive Melanoma via Accumulation of Prematurely Terminated Transcripts

10.1101/824193 ◽

2019 ◽

Author(s):

Megan L. Insco ◽

Brian J. Abraham ◽

Sara J. Dubbury ◽

Sofia Dust ◽

Constance Wu ◽

...

Keyword(s):

Gene Expression ◽

Overall Survival ◽

Rna Polymerase Ii ◽

Kinase Activity ◽

Prognostic Significance ◽

Rna Degradation ◽

Poor Overall Survival ◽

Cyclin Dependent Kinases ◽

Nuclear Rna ◽

Melanoma Patients

AbstractTranscriptional Cyclin Dependent Kinases modulate RNA Polymerase II function to impact gene expression. Here, we show that CDK13 is mutated in 4% of patient melanomas and mutation or downregulation is associated with poor overall survival. Mutant CDK13 lacks kinase activity and overexpression in zebrafish leads to accelerated melanoma. CDK13 mutant fish and human melanomas accumulate prematurely terminated RNAs that are translated into truncated proteins. CDK13 binds to and regulates the phosphorylation of ZC3H14, a member of the PolyA eXosome Targeting (PAXT) RNA degradation complex. ZC3H14 phosphorylation recruits the PAXT complex to degrade prematurely terminated polyadenylated transcripts in the nucleus. In the presence of mutant CDK13, ZC3H14 phosphorylation is compromised and consequently fails to recruit the PAXT complex, leading to truncated transcript stabilization. This work establishes a role for CDK13 and the PAXT nuclear RNA degradation complex in cancer and has prognostic significance for melanoma patients with mutated or downregulated CDK13.

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An RNA-sequencing-based transcriptome for a significantly prognostic novel driver signature identification in bladder urothelial carcinoma

PeerJ ◽

10.7717/peerj.9422 ◽

2020 ◽

Vol 8 ◽

pp. e9422

Author(s):

Danqi Liu ◽

Boting Zhou ◽

Rangru Liu

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Regression Analysis ◽

Urothelial Carcinoma ◽

Cox Regression ◽

Protein Coding ◽

Cox Regression Analysis ◽

Protein Coding Genes ◽

Bladder Urothelial Carcinoma ◽

Rna Signature

Bladder cancer (BC) is the ninth most common malignancy worldwide. Bladder urothelial carcinoma (BLCA) constitutes more than 90% of bladder cancer (BC). The five-year survival rate is 5–70%, and patients with BLCA have a poor clinical outcome. The identification of novel clinical molecular markers in BLCA is still urgent to allow for predicting clinical outcomes. This study aimed to identify a novel signature integrating the three-dimension transcriptome of protein coding genes, long non-coding RNAs, microRNAs that is related to the overall survival of patients with BLCA, contributing to earlier prediction and effective treatment selection, as well as to the verification of the established model in the subtypes identified. Gene expression profiling and the clinical information of 400 patients diagnosed with BLCA were retrieved from The Cancer Genome Atlas (TCGA) database. A univariate Cox regression analysis, robust likelihood-based survival modelling analysis and random forests for survival regression and classification algorithms were used to identify the critical biomarkers. A multivariate Cox regression analysis was utilized to construct a risk score formula with a maximum area under the curve (AUC = 0.7669 in the training set). The significant signature could classify patients into high-risk and low-risk groups with significant differences in overall survival time. Similar results were confirmed in the test set (AUC = 0.645) and in the entire set (AUC = 0.710). The multivariate Cox regression analysis indicated that the five-RNA signature was an independent predictive factor for patients with BLCA. Non-negative matrix factorization and a similarity network fusion algorithm were applied for identifying three molecular subtypes. The signature could separate patients in every subtype into high- and low- groups with a distinct difference. Gene set variation analysis of protein-coding genes associated with the five prognostic RNAs demonstrated that the co-expressed protein-coding genes were involved in the pathways and biological process of tumourigenesis. The five-RNA signature could serve as to some degree a reliable independent signature for predicting outcome in patients with BLCA.

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55 GENE EXPRESSION SIGNATURE ON URINE SAMPLES FOR THE NONINVASIVE DIAGNOSIS AND AGGRESSIVENESS PREDICTION OF BLADDER UROTHELIAL CARCINOMA

European Urology Supplements ◽

10.1016/s1569-9056(10)60063-2 ◽

2010 ◽

Vol 9 (2) ◽

pp. 51

Author(s):

L. Mengual ◽

M. Burset ◽

M.J. Ribal ◽

E. Ars ◽

M. Marfn-Aguilera ◽

...

Keyword(s):

Gene Expression ◽

Urothelial Carcinoma ◽

Gene Expression Signature ◽

Urine Samples ◽

Noninvasive Diagnosis ◽

Expression Signature ◽

Bladder Urothelial Carcinoma

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High SGO2 Expression Predicts Poor Overall Survival: A Potential Therapeutic Target for Hepatocellular Carcinoma

Genes ◽

10.3390/genes12060876 ◽

2021 ◽

Vol 12 (6) ◽

pp. 876

Author(s):

Min Deng ◽

Shaohua Li ◽

Jie Mei ◽

Wenping Lin ◽

Jingwen Zou ◽

...

Keyword(s):

Gene Expression ◽

Hepatocellular Carcinoma ◽

Overall Survival ◽

Therapeutic Target ◽

Tumor Grade ◽

The Cancer Genome Atlas ◽

High Expression ◽

Clinicopathological Parameters ◽

Potential Therapeutic Target ◽

Poor Overall Survival

Shugoshin2 (SGO2) may participate in the occurrence and development of tumors by regulating abnormal cell cycle division, but its prognostic value in hepatocellular carcinoma (HCC) remains unclear. In this study, we accessed The Cancer Genome Atlas (TCGA) database to get the clinical data and gene expression profile of HCC. The expression of SGO2 in HCC tissues and nontumor tissues and the relationship between SGO2 expression, survival, and clinicopathological parameters were analyzed. The SGO2 expression level was significantly higher in HCC tissues than in nontumor tissues (p < 0.001). An analysis from the Oncomine and Gene Expression Profiling Interactive Analysis 2 (GEPIA2) databases also demonstrated that SGO2 was upregulated in HCC (all p < 0.001). A logistic regression analysis revealed that the high expression of SGO2 was significantly correlated with gender, tumor grade, pathological stage, T classification, and Eastern Cancer Oncology Group (ECOG) score (all p < 0.05). The overall survival (OS) of HCC patients with higher SGO2 expression was significantly poor (p < 0.001). A multivariate analysis showed that age and high expression of SGO2 were independent predictors of poor overall survival (all p < 0.05). Twelve signaling pathways were significantly enriched in samples with the high-SGO2 expression phenotype. Ten proteins and 34 genes were significantly correlated with SGO2. In conclusion, the expression of SGO2 is closely related to the survival of HCC. It may be used as a potential therapeutic target and prognostic marker of HCC.

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