scholarly journals A Comprehensive Analysis of the Effect of Histological Subtypes on the Survival Probability of Kidney Carcinoma Patients: A Hypertabastic Survival Analysis

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Tabatabai Mohammad ◽  
Bailey Stephanie ◽  
Matthews-Juarez Patricia ◽  
Tabatabai Habib ◽  
Bahri Nader ◽  
...  
2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Eirini Martinou ◽  
Carla Moller-Levet ◽  
Izhar Bagwan ◽  
Guy Simpson ◽  
Lisiane Meira ◽  
...  

Abstract Aims Pre-B-cell Leukaemia (PBX) genes are important in organ development during embryogenesis. To date, four members of the PBX family (PBX1, PBX2, PBX3, PBX4) have been identified to be involved in human cancers, but little is known about their role in colorectal cancer (CRC). The aim of this study was to determine their differential expression, prognostic role and function in CRC. Methods Molecular and overall survival (OS) data from 614 patients with CRC were obtained from the National Cancer Institute, Tissue Cancer Genome Atlas (TCGA) database. To investigate the differential PBX gene mRNA expression, we performed a comparative cancer to normal computational analysis in edgeR. To determine PBXs prognostic value, we conducted Kaplan-Meier survival analysis and COX regression, selecting 10-year OS as primary outcome. Lastly, to explore the effect of PBX4 in CRC cell growth and angiogenesis, we performed gene expression modulation experiments using a PBX4-overexpressing plasmid-vector. Cell proliferation and VEGFA angiogenic factor expression were defined as primary and secondary in vitro outcomes respectively. Results Among PBXs only PBX4 was significantly upregulated showing a 4-fold increase in CRC vs normal colon (p < 0.0001). Survival analysis showed that only high PBX4 mRNA expression was associated with increased risk for worse OS in patients with CRC (HR:1.3 95%CI:1-1.6, p = 0.02). Functionally, overexpression of PBX4 significantly increased CRC cell proliferation in vitro (p < 0.001) and markedly upregulated the expression of VEGFA (p < 0.0001). Conclusions Comprehensive analysis of the PBX gene family identifies that PBX4 may function as a novel oncogene and may promote angiogenesis through VEGFA in CRC.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Tanja Mesti ◽  
Vid Ceplak Mencin ◽  
Biljana Mileva Boshkoska ◽  
Janja Ocvirk

Abstract Background Immunotherapy with CTLA-4 inhibitors and PD1 checkpoint inhibitors has initiated a breakthrough in the treatment and prognosis of patients with metastatic melanoma. The survival of these patients has increased from the expected survival time of less than 12 months to at least forty months. However, immunotherapy with either anti-CTLA-4 antibodies or PD1 inhibitors alone or in combination has a broad palette of significant immune-related adverse events. The aim of the study was to assess the correlation of immune-related adverse events with treatment outcomes defined as significant differences in the overall response rate (ORR) and progression-free survival (PFS) of patients, who developed immune-related adverse events during immunotherapy. Patients and methods A retrospective analysis of patients with metastatic melanoma treated with immunotherapy in 2020 at the Oncology Institute of Ljubljana was performed. Only patients with radiological evaluation of the immunotherapy response were included. The patients were divided into two cohorts: a cohort of patients with immune-related adverse events (irAE group) and a cohort of patients with no immune-related adverse events (NirAE group). Significantly better overall response and progression-free survival in the irAE cohort defined the primary aim of our study. To investigate the differences in progression-free survival between the irAE cohort and NirAE cohort, we used survival analysis. In particular, a Cox proportional hazards model with covariates of time to progression and adverse events was used for survival analysis. The Kruskal-Wallis H-test was applied, and a p-value of p <= 0.05 was considered the cut-off point for a statistically significant difference between the groups. Results Among the 120 patients treated with immunotherapy, radiological response evaluation was performed for 99 patients: 38 patients in the irAE cohort and 61 patients in the NirAE cohort. The ORRs for the irAE and NirAE cohorts were 57% and 37%, respectively. The PFS was significantly better for the irAE cohort (301.6 days) than for the NirAE cohort (247.29 days). The results of the survival regression analysis showed a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort. Conclusions Patients with metastatic melanoma treated with immunotherapy who developed immune-related adverse events showed better treatment outcomes with longer times to disease progression and better overall response rates than patients treated with immunotherapy who did not develop immune-related adverse events, with a significant increase in the survival probability from less than 60% for the NirAE cohort to almost 80% for the irAE cohort.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1275-1275
Author(s):  
Maren Gaudig ◽  
István Vályi-Nagy ◽  
Peter Takacs ◽  
Miklos Bacskai ◽  
Petra Kozma ◽  
...  

Abstract Background: Real-world evidence based analyses are gaining importance worldwide. They are especially useful to inform medical/scientific evidence setting, health policy decision-making, or health-economic modelling. Due to legislation for data of public interest set in Act LXIII of 2012, health care data recorded by the predominantly state-owned health insurance system are accessible in Hungary. The National Health Insurance Fund Administration (NHIFA) as single payer covers the total population of 10 million inhabitants, providing de-identified patient data on health care resource utilization and demographics upon request. Chronic lymphocytic leukaemia is an adult haematological malignancy. New therapies, e.g. BTKs need to find their place in therapy but the currently available information in Hungary on epidemiology, patient pathways and characteristics on population level are scarce. Aim: During the last decade numerous novel therapeutic options became available. Mortality as an important treatment outcome is of interest to understand any impact these novel agents may have. We evaluated overall survival during the period from 2000 – 2013 with the hypothesis that survival rate is strongly correlated with time of first diagnosis and subsequently availability of appropriate therapies. Methods: As part of a larger project called LYRICS (Lymphoma Real-Life Insight Core Survey) we have conducted a comprehensive retrospective analysis based on the NHIFA's database to map the CLL therapy landscape and outcomes in the last 14 years. The basis of the analysis was the claims database of inpatient and outpatient care (DRG based financing) and outpatient drug reimbursement system. Mortality rates were studied by non-parametric (Kaplan-Meier survival analysis) and semi-parametric (Cox proportional hazard regression) approaches. Results:The annual number of prevalent CLL patients is 3-4,000 with 8-900 newly diagnosed patients annually. The assessment was based on at least two relevant and confirmed C91.10 ICD diagnoses in inpatient or outpatient care. Kaplan-Meier curve estimates show the median overall survival from diagnosis is 80 months. The survival probability at one elapsed year is 91% in CLL patients diagnosed between the years 2002-2013, and 95% in the years between 2007-2013. The 4-year survival probability is 67% for patients diagnosed between the years of 2002-2013 and 78% for patients diagnosed between the years 2007-2013 (Figure 1 below). By fitting Cox model with age covariates, it can be shown that there is significant difference in relative risk (RR) of death in different age cohorts. The RR of death in the 60-69 age cohort is 1.5 times and in the 70-79 age cohort is more than 2 times higher than in the 50-59 age cohort of CLL patients. Figure 1 Survival analysis from first diagnosis by Kaplan-Meier method Figure 1. Survival analysis from first diagnosis by Kaplan-Meier method Conclusion: These results from this analyses show a significant increase of survival in Hungary over the last 15 years. The availability of treatment options have contributed to this increased survival probability. This population, real-world data confirms the relevance of age at first diagnosis as predictor for overall survival. Recently approved therapies in CLL, e.g. Ibrutinib are expected to further improve the mortality outcome for this patient group. Disclosures Gaudig: Janssen : Employment. Vályi-Nagy:Janssen-Cilag Ltd.: Consultancy. Takacs:Janssen-Cilag Ltd. Hungary: Employment. Bacskai:Healthware Consulting Ltd: Equity Ownership. Kozma:Janssen-Cilag Ltd. Hungary: Employment. Rakonczai:Healthware Consulting Ltd: Employment. Püspöki:Healthware Consulting Ltd: Employment.


2020 ◽  
Author(s):  
Chen Li ◽  
Fang Yan ◽  
Gang Chen ◽  
Qiang Li ◽  
Hua Xian ◽  
...  

Abstract Background: Cervical squamous cell cancer (CESC) is a common malignancy tumor with high incidence and mortality in women globally. Increasing studies have indicated that there was an indivisible association between alternative mRNA splicing (AS) and multiple types of cancer. However, comprehensive analysis of alternative mRNA splicing events is scarce in CESC. Methods: In this study, alternative mRNA splicing events data and clinical information of 216 CESC patients were downloaded from TCGA SpliceSeq database and TCGA website. We used identified survival-associated splicing events (SASEs) to construct prognostic signatures. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve were performed to evaluate the clinical value of prognostic signatures. A nomogram was carried out to quantitatively predict individuals’ survival probability. Regulatory network between splicing factors (SFs) and SASE was analyzed to explore the upstream regulators of a certain SASE. Additionally, we explored potential downstream pathways of a certain SASE. Results: A total of 41776 alternative splicing events in 9961 genes were collected. After sorting out SASEs, multivariable regression analysis was used to acquire 70 SASEs that could be independent prognostic factors for overall survival in CESC. Kaplan-Meier survival analyses showed that the difference was statistically significant (P<0.01). The area under ROC curve (AUC) for all AS pattern was 0.932. A nomogram was constructed with a concordance index of 0.82 to predict individuals’ survival probability. EIF3A positively regulated SEC23A-27346-AP with highest correlation coefficient (P<0.001, R=0.69). Besides, the most significant SASEs and KEGG pathways were SEC23A-27346-AP and adherens junction pathway (P=0.02, R=0.65). Conclusions: Prognostic signatures of survival-associated splicing events were independent prognostic factors for overall survival among CESC patients. A nomogram could quantitatively predict individuals’ survival probability. Moreover, we proposed that splicing factor EIF3A positively regulated SEC23A-27346-AP, and adherens junction pathway may be the downstream pathway of SEC23A-27346-AP. The aforementioned signaling pathway could play a crucial role in the development of CESC.


2021 ◽  
Vol 9 (1) ◽  
pp. 215-226
Author(s):  
Umut Türk ◽  
Serap Sap

This research investigates the survival probability of listings in the Airbnb platform during the COVID-19 period between January-October 2020 in Istanbul. In line with the research aim, Cox's Proportional Hazard Model is adopted to conduct survival analysis, where the physical and spatial attributes of Airbnb listings are used as predictors. Our findings show that while physical attributes show similarity to previous findings, spatial attributes show substantial differences in the Pre-COVID and Post-COVID comparison.  The contributions of the study have two facets. Theoretically, this research's findings contribute to the current literature by understanding the changing consumer preferences and identifying the factors that affect Airbnb listings' survival rates during the COVID-19 pandemic. The findings may also help practitioners understand changing customers' preferences during COVID, especially in terms of locational choices. Moreover, customer feedback's quality and quantity might help the Airbnb hosts to improve their service quality, attract more customers, and be more resilient under the changing conditions.


2008 ◽  
Vol 49 (7) ◽  
pp. 1403-1406 ◽  
Author(s):  
Catherine Thieblemont ◽  
Delphine Rolland ◽  
Lucile Baseggio ◽  
Pascale Felman ◽  
Sophie Gazzo ◽  
...  

2020 ◽  
Author(s):  
Hui Shen ◽  
Huan Pan ◽  
Jianju Lu ◽  
Jianfen Shen ◽  
Longsheng Xu ◽  
...  

Abstract BackgroundThere is increasing evidence that circular RNA (circRNA) is closely related to tumorigenesis and cancer progression. circRNA has been identified as a sponge of microRNA (miRNA) in a competitive endogenous RNA (ceRNA) network and is involved in the regulation of mRNA expression. However, the roles of cancer specific circRNAs in circRNA-related ceRNA network of breast cancer (BRCA) are still unclear. This study aims to construct a ceRNA network associated with circRNA and to explore new therapeutic and prognostic targets and biomarkers for breast cancer.MethodsWe downloaded the circRNA expression profile of BRCA from Gene Expression Omnibus (GEO) microarray datasets and downloaded the miRNA and mRNA expression profiles of BRCA from The Cancer Genome Atlas (TCGA) database, these data were included in the study for comprehensive analysis. Differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed circRNAs (DEcircRNAs) were identified and a competitive endogenous RNA (ceRNA) regulatory network was constructed based on circRNA–miRNA pairs and miRNA–mRNA pairs. Gene ontology and pathway enrichment analysis were performed on mRNAs regulated by circRNAs in ceRNA networks. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network were performed. The STRING search tool was used to predict the interaction between proteins, and the hub genes were screened by the MCODE plugin in Cytoscape.ResultsA total of 72 DEcircRNAs, 158 DEmiRNAs and 2762 DE mRNAs were identified. The constructed ceRNA network contains 60 circRNA-miRNA pairs and 140 miRNA-mRNA pairs, including 40 circRNAs, 30 miRNAs and 100 mRNAs. Functional enrichment indicated that DEmRNAs regulated by DEcircRNAs in ceRNA networks were significantly enriched in PI3K-Akt signaling pathway, MicroRNAs in cancer and Proteoglycans in cancer. Survival analysis and correlation analysis of all mRNAs and miRNAs in the ceRNA network showed that a total of 13 mRNAs and 6 miRNAs were significantly associated with overall survival, and 48 miRNA-mRNA interaction pairs had a significant negative correlation. A PPI network was established and 21 hub genes were determined from the network. After comprehensive analysis, four potential ceRNA regulatory axes were constructed based on three circRNAs, two miRNAs, and three mRNAs.ConclusionsThis study provides an effective bioinformatics basis for further understanding the molecular mechanisms and predictions of breast cancer. A better understanding of the circRNA-related ceRNA network in BRCA will help identify potential biomarkers for diagnosis and prognosis.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiaotao Li ◽  
Shi Fu ◽  
Yinglong Huang ◽  
Ting Luan ◽  
Haifeng Wang ◽  
...  

Abstract Background Bladder cancer (BC) is one of the most common malignancies and has a relatively poor outcome worldwide. In this study, we attempted to construct a novel metabolism-related gene (MRG) signature for predicting the survival probability of BC patients. Methods First, differentially expressed MRGs between BC and normal samples were identified and used to construct a protein-protein interaction (PPI) network and perform mutation analysis. Next, univariate Cox regression analysis was utilized to select prognostic genes, and multivariate Cox regression analysis was applied to establish an MRG signature for predicting the survival probability of BC patients. Moreover, Kaplan-Meier (KM) survival analysis and receiver operating characteristic (ROC) analysis were performed to evaluate the predictive capability of the MRG signature. Finally, a nomogram based on the MRG signature was established to better predict the survival of BC. Results In the present study, 27 differentially expressed MRGs were identified, most of which presented mutations in BC patients, and LRP1 showed the highest mutation rate. Next, an MRG signature, including MAOB, FASN and LRP1, was established by using univariate and multivariate Cox regression analysis. Furthermore, survival analysis indicated that BC patients in the high-risk group had a dramatically lower survival probability than those in the low-risk group. Finally, Cox regression analysis showed that the risk score was an independent prognostic factor, and a nomogram integrating age, pathological tumor stage and risk score was established and presented good predictive ability. Conclusion We successfully constructed a novel MRG signature to predict the prognosis of BC patients, which might contribute to the clinical treatment of BC.


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