Prognostic value of hypoxia gene expression in bladder cancer patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 548-548
Author(s):  
Hyun Chang ◽  
Seung-Hyun Lee ◽  
Taeryool Koo ◽  
Moon Ho Kim ◽  
Soo-Yoon Sung

548 Background: The prognostic value of hypoxia in bladder cancer remains unknown. We aimed to evaluate the potential role of hypoxia gene signature as prognostic factors in bladder cancer patients. Methods: We investigated the hypoxia gene signature and clinicopathologic features of The Cancer Genome Atlas (TCGA) bladder urothelial carcinoma (n = 408) using the Kaplan-Meier survival curves and multivariate Cox regression analyses. The clinicopathologic data and the processed data of hypoxia gene signature were obtained from TCGA Bladder urothelial carcinoma database. Results: Hypoxia gene signature score was significantly associated with overall survival (OS) and progression-free survival (PFS). Higher score resulted in shorter OS and PFS in Kaplan-Meier survival curves with Log-rank test ( P < 0.01 and P <0.05, respectively). In multivariate analysis containing clinical prognostic variables, higher hypoxia gene signature score predicted poor OS (adjusted HR= 1.58, 95% CI 1.15 - 2.19; P <0.01). Conclusions: Hypoxia gene signature was an independent prognostic factor in bladder cancer. Prospective studies are needed to evaluate the prognostic role of hypoxia in bladder cancer patients.

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7836 ◽  
Author(s):  
Rui Zhu ◽  
Xin Yang ◽  
Wenna Guo ◽  
Xin-Jian Xu ◽  
Liucun Zhu

Background Bladder cancer is one of the most common cancers, and its histopathological type is mainly bladder urothelial carcinoma, accounting for about 90%. The prognostic biomarkers of bladder cancer are classified into clinical features biomarkers and molecular biomarkers. Nevertheless, due to the existence of individual specificity, patients with similar pathological characteristics still have great differences in the risk of disease recurrence. Therefore, it is often inaccurate to predict the survival status of patients based on clinical characteristic biomarkers, and a prognostic molecular biomarker that can grade the risk of bladder cancer patients is needed. Methods A total of three bladder urothelial carcinoma datasets were used in this study from the Cancer Genome Atlas database and Gene Expression Omnibus database. In order to avoid overfitting, all samples were randomly divided into one training set and three validation sets, which were used to construct and test the prognostic biomarker model of bladder urothelial carcinoma. Univariate and multivariate Cox regression were used to screen candidate mRNAs and construct prognostic biomarkers model. Kaplan–Meier survival analysis and the receiver operating characteristic (ROC) curve were used to evaluate the predictive performance of the model. Results A prognostic biomarker model of bladder urothelial carcinoma combining with eight mRNA was constructed. Kaplan–Meier analyses indicated that a significant difference in the survival time of patients between the high-risk and the low-risk group. The area under the ROC curve were 0.632 (95% confidence interval (CI) [0.541–0.723]), 0.693 (95% CI [0.601–0.784]) and 0.686 (95% CI [0.540–0.831]) when the model was used to predict the patient’s survival time in three validation datasets. The model showed high accuracy and applicability.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Cosphiadi Irawan ◽  
Andhika Rachman ◽  
Puji Rahman ◽  
Arif Mansjoer

Background. The three-year survival rate of locally advanced nasopharyngeal carcinoma (NPC) patients in Indonesia is lower than in other Asian countries. Calculation of hemoglobin-to-platelet ratio (HPR) may become a more practical predictor than the ratios using leukocyte cell components. Yet, no study has been conducted to investigate the potential of HPR in predicting survival outcomes in locally advanced nasopharyngeal cancer patients. Objective. To determine the role of pretreatment hemoglobin-to-platelet ratio in predicting the three-year overall survival (OS) of locally advanced NPC. Method. A retrospective cohort study followed up on 289 locally advanced NPC patients who had undergone therapy at the Dr. Cipto Mangunkusumo National General Hospital between January 2012 and October 2016. HPR cut-off was determined using ROC. Subjects were classified into two groups according to the HPR value. Kaplan-Meier curve was utilized to illustrate patients’ three-year survival, and Cox regression test analyzed confounding variables to yield an adjusted hazard ratio (HR). Results. The optimal cut-off for HPR was 0.362 (AUC 0.6228, 95% CI: 0.56-0.69, sensitivity 61.27%, specificity 60.34%). Of the subjects, 48.44% had HPR ≤ 0.362 , and they had a higher three-year mortality rate than those with HPR > 0.362 (50% vs. 31.54%). In bivariate analysis, HPR ≤ 0.362 and age ≥ 60 significantly showed a worse three-year OS ( p value = 0.003 and 0.075, respectively). In multivariate analysis, we concluded that a pretreatment HPR ≤ 0.362 was an independent negative predictor of three-year OS in locally advanced NPC patients (adjusted HR 1.82; 95% CI: 1.25–2.65). Conclusion. Pretreatment HPR ≤ 0.362 was a negative predictor of three-year OS in locally advanced nasopharyngeal cancer patients.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5511-5511
Author(s):  
Rebeca Lozano ◽  
Elena Castro ◽  
Isabel Aragon ◽  
Heather Thorne ◽  
Fernando López-Campos ◽  
...  

5511 Background: Germline BRCA1/2 (g BRCA1/2) mutations are associated with poor clinical outcomes in PC. Previous studies showed that g BRCA2 carriers present more CNV in several genes associated with more aggressive disease. These aberrations may explain the poor clinical outcomes of these patients, but larger studies are needed to confirm these findings. Methods: PROREPAIR-A is a multicenter case-control study in which g BRCA2 carriers with available diagnostic timor-tissue were matched 1:2 by Gleason and stage at diagnosis (M0 vs M1) with known non-carriers (NC). A minimum of 120 controls-60 cases were required to prove a 5yr Cause Specific Survival (CSS)-rate of 85% vs 60%. The primary endpoint was to confirm the independent prognostic value of g BRCA2 in PC CSS. In addition, we explored the prognostic role of g BRCA1 and somatic events in BRCA2, RB1, MYC, PTEN and TMPRSS2-ERG by FISH. Χ2, Kaplan-Meier, log-rank and cox-regression models were carried out to identify associations with baseline characteristics and outcomes: Metastases Free Survival (MFS), Time to Castration-Resistance (TTCR) and CSS. Results: A total of 80:160 matched cases-controls were initially included, but tumor tissue and clinical data were only available in 73 g BRCA2 and 127 NC. 14 g BRCA1 were also included. At diagnosis, g BRCA2 were younger (median 62.6 vs 64.5, p = 0.02) and had cT3-4 disease more often than NC (31.5% vs 9.4%, p < 0.01), but no other significant differences were found. Somatic BRCA2-RB1 codeletion (40.8% vs 11.8%, p < 0.01) and MYC amplification (51.4% vs 22.8%, p < 0.01) were more frequent in g BRCA2 compared to NC, but no significant differences in PTEN and TMPRSS2-ERG were observed. g BRCA2 mutations as well as somatic BRCA2-RB1 codel and MYC amplif were significantly associated with shorter CSS, MFS and TTCR (Table). MVA model confirmed the independent prognostic value of g BRCA2 (HR 1.94, p = 0.03), BRCA2-RB1 codel (HR 3.16, p < 0.01), MYC amplif (HR 2.36, p < 0.01), Gleason ≥8 (p < 0.01) and M1 at diagnosis (p < 0.01) for CSS. Conclusions: PROREPAIR-A confirmed the independent prognostic value of g BRCA2 for CSS. Somatic BRCA2, RB1 and MYC aberrations were more frequent in g BRCA2 carriers. Those alterations are associated with shorter CSS, MFS and TTCR, and may contribute to poor clinical outcomes in g BRCA2 and NC. [Table: see text]


2021 ◽  
Vol 12 ◽  
Author(s):  
Yunhe Han ◽  
Cunyi Zou ◽  
Chen Zhu ◽  
Tianqi Liu ◽  
Shuai Shen ◽  
...  

Objective: Nectin and nectin-like molecules (Necls) are molecules that are involved in cell–cell adhesion and other vital cellular processes. This study aimed to determine the expression and prognostic value of nectin and Necls in low grade glioma (LGG).Materials and Methods: Differentially expressed nectin and Necls in LGG samples and the relationship of nectin family and Necls expression with prognosis, clinicopathological parameters, and survival were explored using The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and Repository of Molecular Brain Neoplasia Data (REMBRANDT) databases. Univariate and multivariate Cox analysis models were performed to construct the prognosis-related gene signature. Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves and multivariate Cox regression analysis, were utilized to evaluate the prognostic capacity of the four-gene signature. Gene ontology (GO)enrichment analysis and Gene Set Enrichment Analyses (GSEA) were performed to further understand the underlying molecular mechanisms. The Tumor Immune Estimation Resource (TIMER) was used to explore the relationship between the four-gene signature and tumor immune infiltration.Results: Several nectin and Necls were differentially expressed in LGG. Kaplan–Meier survival analyses and Univariate Cox regression showed patients with high expression of NECTIN2 and PVR and low expression of CADM2 and NECTIN1 had worse prognosis among TCGA, CGGA, and REMBRANDT database. Then, a novel four-gene signature was built for LGG prognosis prediction. ROC curves, KM survival analyses, and multivariate COX regression indicated the new signature was an independent prognostic indicator for overall survival. Finally, GSEA and GO enrichment analyses revealed that immune-related pathways participate in the molecular mechanisms. The risk score had a strong negative correlation with tumor purity and data of TIMER showed different immune cell proportions (macrophage and myeloid dendritic cell) between high- and low-risk groups. Additionally, signature scores were positively related to multiple immune-related biomarkers (IL 2, IL8 and IFNγ).Conclusion: Our results offer an extensive analysis of nectin and Necls levels and a four-gene model for prognostic prediction in LGG, providing insights for further investigation of CADM2, NECTIN1/2, and PVR as potential clinical and immune targets in LGG.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9422
Author(s):  
Danqi Liu ◽  
Boting Zhou ◽  
Rangru Liu

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.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 376-376 ◽  
Author(s):  
Shreyas Joshi ◽  
Elizabeth Handorf ◽  
Andres Correa ◽  
Alexander Kutikov ◽  
Benjamin T. Ristau ◽  
...  

376 Background: Histological variants of urothelial carcinoma (UC) of the bladder have a poorer prognosis than histologically pure UC, and the role of neoadjuvant chemotherapy (NAC) in this group is unclear. Our objective was to evaluate NAC practice patterns and survival outcomes in patients with histologic variants undergoing radical cystectomy (RC). Methods: Patients with cT2-4N0-3M0 muscle invasive bladder cancer (MIBC) who underwent RC from 2003-2012 were selected from the National Cancer Database (NCDB). Patients were categorized by histology code as pure UC or histologic variants. Adjusting for patient and clinical characteristics, generalized estimating equations were used to test the association between histology and receipt of NAC. The association between receipt of NAC and overall survival (OS) was evaluated using Kaplan Meier curves and Cox regression models. Results: In 19,976 patients meeting inclusion criteria, receipt of NAC in histologic variants was less (11-14%) than in pure UC (22%), with the exception of micropapillary disease (23%) (Table). Median OS was lower in variant histologies than for pure UC (8.4 – 30.2 vs. 37.6 months). Receipt of NAC was associated with improved survival compared to RC or RC+adjuvant chemotherapy in patients with pure UC (HR 0.91, p=0.0016). There was no evidence of a survival benefit for NAC in the variant histologies, or that treatment effects differed by histology (P-val for interaction=0.84). Conclusions: In the NCDB, a substantial proportion of patients (13%) with histologic variants of MIBC undergoing RC receive NAC in the absence of a proven survival benefit. Clinical trials inclusive of patients with variant histologies are necessary to elucidate the role of NAC prior to RC. [Table: see text]


2021 ◽  
pp. 106689692110272
Author(s):  
Jennifer B. Gordetsky ◽  
Kathleen W. Montgomery ◽  
Giovanna A. Giannico ◽  
Soroush Rais-Bahrami ◽  
Prabin Thapa ◽  
...  

Objectives. To compare the clinicopathologic characteristics of urothelial carcinoma (UC), urothelial carcinoma with squamous differentiation (UCSD), and squamous cell carcinoma (SCC) of the bladder, which have been suggested to differ in terms of risk factors, immunophenotype, and prognosis. Methods. We evaluated the clinicopathologic features of radical cystectomy specimens between 1980 and 2015 with a diagnosis of SCC, UCSD, and UC. PD-L1 immunohistochemistry (clinically available clones 22C3, SP142, and SP263) was performed on SCC and UCSD. Multivariate Cox regression was used to identify prognostic factors. Kaplan–Meier curves were plotted to assess cancer-specific survival (CSS). Results. Of the 1478 cases, there were 1126 UC (76%), 217 UCSD (15%), and 135 SCC (9%). Bladder cancer was more common in men than women (80% vs 20%, P < .0001). However, a higher proportion of SCC and UCSD occurred in women (SCC-36%, UCSD-22%, UC-18%). Women were significantly more likely to be never smokers in all 3 cohorts (UC: 45% vs 16%, UCSD: 44% vs 12%, SCC: 40% vs 18%, P < .0001). Patients with SCC and UCSD were at a higher pathologic stage (>pT2) at the time of cystectomy (UCSD-74%, SCC 71%, UC-44%, P < .0001) and had worse CSS compared to patients with UC ( P = 0.006). SCC had higher PD-L1 scores (all clones) than UCSD ( P < .0001). PD-L1 22C3 ( P = .02, HR: 0.36) and SP142 scores ( P = .046, HR: 0.27) predicted CSS on Kaplan–Meier analysis for SCC cases. Conclusions. UC, UCSD, and SCC are associated with different risk factors, gender distributions, and clinical outcomes. PD-L1 is expressed in SCC and UCSD, suggesting some patients may benefit from targeted therapy.


2020 ◽  
Author(s):  
Lili Wang ◽  
Hongguang Song ◽  
Shiming Yang

Abstract Background: miR-27a-3p has been found dysexpressed in various cancers. The aim of the present study was to clarify the prognostic value of miR-27a-3p in patients with oral cancer.Methods: We used quantitative real-time polymerase chain reaction (qRT-PCR) assay to detect the expression of miR-27a-3p in the tissue of oral cancer and adjacent normal specimens. The association of miR-27a-3p with clinicopathological characteristics was analyzed via the Chi-square test. Kaplan-Meier survival and Cox regression analysis were performed to evaluate the prognostic value of miR-27a-3p in oral cancer patients.Results: The down-regulated expression of miR-27a-3p was found in oral cancer tissues compared with the matched noncancerous samples (P<0.05). And its expression was influenced by TNM stage (P=0.032), T stage (P=0.014) and lymph node metastasis (P=0.025). Kaplan–Meier analysis result showed that the decreased level of miR-27a-3p expression was associated with a poor overall survival of oral cancer patients. Additionally, multivariate cox regression analysis revealed that the low expression of miR-27a-3p was an independent prognostic maker in oral cancer patients (HR=0.462, 95% CI=0.223-0.957, P=0.038).Conclusions: Taken together, the expression pattern of miR-27a-3p was decreased in oral cancer tissues. The decreased expression of miR-27a-3p was a potential prognostic biomarker in patients with oral cancer.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Feng ◽  
Jinping Zhou ◽  
Lin Zhao ◽  
Xinpeng Wang ◽  
Danyu Ma ◽  
...  

Glioma is a relatively low aggressive brain tumor. Although the median survival time of patients for lower-grade glioma (LGG) was longer than that of patients for glioblastoma, the overall survival was still short. Therefore, it is urgent to find out more effective molecular prognostic markers. The role of the Fam20 kinase family in different tumors was an emerging research field. However, the biological function of Fam20C and its prognostic value in brain tumors have rarely been reported. This study aimed to evaluate the value of Fam20C as a potential prognostic marker for LGG. A total of 761 LGG samples (our cohort, TCGA and CGGA) were included to investigate the expression and role of Fam20C in LGG. We found that Fam20C was drastically overexpressed in LGG and was positively associated with its clinical progression. Kaplan-Meier analysis and a Cox regression model were employed to evaluate its prognostic value, and Fam20C was found as an independent risk factor in LGG patients. Gene set enrichment analysis also revealed the potential signaling pathways associated with Fam20C gene expression in LGG; these pathways were mainly enriched in extracellular matrix receptor interactions, cell adhesion, cell apoptosis, NOTCH signaling, cell cycle, etc. In summary, our findings provide insights for understanding the potential role of Fam20C and its application as a new prognostic biomarker for LGG.


2022 ◽  
Vol 11 ◽  
Author(s):  
Xiya Jia ◽  
Bing Chen ◽  
Ziteng Li ◽  
Shenglin Huang ◽  
Siyuan Chen ◽  
...  

BackgroundGastric cancer (GC) is a highly molecular heterogeneous tumor with poor prognosis. Epithelial-mesenchymal transition (EMT) process and cancer stem cells (CSCs) are reported to share common signaling pathways and cause poor prognosis in GC. Considering about the close relationship between these two processes, we aimed to establish a gene signature based on both processes to achieve better prognostic prediction in GC.MethodsThe gene signature was constructed by univariate Cox and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses by using The Cancer Genome Atlas (TCGA) GC cohort. We performed enrichment analyses to explore the potential mechanisms of the gene signature. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) curves were implemented to assess its prognostic value in TCGA cohort. The prognostic value of gene signature on overall survival (OS), disease-free survival (DFS), and drug sensitivity was validated in different cohorts. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) validation of the prognostic value of gene signature for OS and DFS prediction was performed in the Fudan cohort.ResultsA prognostic signature including SERPINE1, EDIL3, RGS4, and MATN3 (SERM signature) was constructed to predict OS, DFS, and drug sensitivity in GC. Enrichment analyses illustrated that the gene signature has tight connection with the CSC and EMT processes in GC. Patients were divided into two groups based on the risk score obtained from the formula. The Kaplan-Meier analyses indicated high-risk group yielded significantly poor prognosis compared with low-risk group. Pearson’s correlation analysis indicated that the risk score was positively correlated with carboplatin and 5-fluorouracil IC50 of GC cell lines. Multivariate Cox regression analyses showed that the gene signature was an independent prognostic factor for predicting GC patients’ OS, DFS, and susceptibility to adjuvant chemotherapy.ConclusionsOur SERM prognostic signature is of great value for OS, DFS, and drug sensitivity prediction in GC, which may give guidance to the development of targeted therapy for CSC- and EMT-related gene in the future.


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