Determining the Correlation Between the TP53 Gene and Kidney Cancer Survival Through the Cox Proportional-Hazards Regression Model

Significant Difference

Kidney cancer is among the most common and deadly forms of cancer and its incidence has spiked considerably in recent years. It contains a high propensity to rapidly spread to nearby organs, making swift and early diagnosis absolutely critical to ensuring optimal patient recovery. However, its subtle symptoms and manifestation in laboratory tests can make discerning its occurrence difficult. Predicting the probability of the carcinoma based upon various gene mutations has been previously explored, but this study specifically focuses on the TP53 mRNA and the effect its variants have. The Cox proportional-hazards regression technique, ubiquitously regarded as the most accurate method for survival modeling, is utilized to determine that there is a statistically significant difference in the renal cell carcinoma survival of patients with and without the TP53 gene expression. Specifically, possessing this gene, which itself encodes a tumor suppressor protein, correlates with a much higher survival rate from the carcinoma. This finding contains large implications for future exploration within the intersection of genomics and oncology and suggests the efficacy of gene prediction in carcinomas and other pathologies with hereditary predilections.

Utilization and sequencing of targeted therapy and cytoreductive nephrectomy in non–clear cell metastatic kidney cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.615 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 615-615

Author(s):

Liam Connor Macleod ◽

Scott S. Tykodi ◽

Sarah Holt ◽

John L. Gore

Keyword(s):

Overall Survival ◽

Targeted Therapy ◽

Kidney Cancer ◽

Proportional Hazards ◽

Clear Cell ◽

Average Treatment Effect ◽

Targeted Agents ◽

615 Background: Many patients with metastatic kidney cancer (mRCC) are ineligible for trials due to non-clear cell histology. Efficacy of targeted therapy agents in non-clear cell mRCC is still being investigated. We hypothesized that sequencing CN upfront is associated with improved overall survival. We analyze a population-based cohort of non-clear cell mRCC patients in the targeted therapy era. Methods: Patients from the SEER-Medicare files (2005-2011) with non-clear cell mRCC were categorized as having received upfront targeted therapy or upfront CN. Additional exclusions were age < 66 to avoid confounding by uncaptured non-Medicare coverage, and competing stage IV cancer. Targeted therapy was identified through Medicare Part D files. Cox proportional hazards regression determined association between treatment groups, clinical and cancer-related characteristics, and the main outcome, median overall survival (OS). Propensity matching controlled for measurable confounding in treatment selection. Results: Of 1,326 mRCC cases, 528 met inclusion criteria of whom 433 (82%) received targeted agents and 172 (33%) underwent CN. Of those not having CN, 74% were diagnosed by biopsy, 10% by cytology, and 16% radiographically (confirmed at autopsy). Thirteen percent received CN then targeted therapy (OS 14 mos, IQR 9-25), 2.5% received targeted therapy then CN (OS 14 mos, IQR 9-26), 18% received CN only (OS 14 mos, IQR5-40), 67% received targeted therapy only (OS 9 mos, IQR 4-19). On multivariable Cox proportional hazards regression upfront CN (regardless of post-CN therapy) was associated with improved OS (HR 0.54,95% CI 0.41,0.72). Using propensity scores, upfront CN patients (N = 161) were matched to upfront targeted therapy patient (N = 111) and the average treatment effect of CN was 8.3 months survival improvement (95% CI 4.0, 13.2). Conclusions: Although utilization of targeted agents in non-clear cell mRCC exceeds 80%, those with greatest OS received CN either upfront or after targeted therapy, though the latter was rare (2.5%). The variety of sequencing strategies observed is evidence of uncertainty regarding the best care for non-clear cell mRCC patients given limited options.

Novel head and neck cancer survival analysis approach: Random survival forests versus cox proportional hazards regression

Head & Neck ◽

10.1002/hed.21698 ◽

2011 ◽

Vol 34 (1) ◽

pp. 50-58 ◽

Cited By ~ 24

Author(s):

Frank R. Datema ◽

Ana Moya ◽

Peter Krause ◽

Thomas Bäck ◽

Lars Willmes ◽

...

Keyword(s):

Head And Neck Cancer ◽

Survival Analysis ◽

Head And Neck ◽

Cancer Survival ◽

Proportional Hazards ◽

Random Survival Forests ◽

Survival Forests

Replacement of potatoes with other vegetables and risk of myocardial infarction in the Danish Diet, Cancer and Health cohort

British Journal Of Nutrition ◽

10.1017/s0007114521000349 ◽

2021 ◽

pp. 1-21

Author(s):

Anne Mette L. Würtz ◽

Mette D. Hansen ◽

Anne Tjønneland ◽

Eric B. Rimm ◽

Erik B. Schmidt ◽

...

Keyword(s):

Myocardial Infarction ◽

Similar Pattern ◽

Proportional Hazards ◽

Heterogeneous Group ◽

Dietary Guidelines ◽

Root Vegetables

ABSTRACT Intake of vegetables is recommended for the prevention of myocardial infarction (MI). However, vegetables make up a heterogeneous group, and subgroups of vegetables may be differentially associated with MI. The aim of this study was to examine replacement of potatoes with other vegetables or subgroups of other vegetables and the risk of MI. Substitutions between subgroups of other vegetables and risk of MI were also investigated. We followed 29,142 women and 26,029 men aged 50-64 years in the Danish Diet, Cancer and Health cohort. Diet was assessed at baseline by using a detailed validated FFQ. Hazards ratios (HR) with 95% CI for the incidence of MI were calculated using Cox proportional hazards regression. During 13.6 years of follow-up, 656 female and 1,694 male cases were identified. Among women, the adjusted HR for MI was 1.02 (95% CI: 0.93, 1.13) per 500 g/week replacement of potatoes with other vegetables. For vegetable subgroups, the HR was 0.93 (95% CI: 0.77, 1.13) for replacement of potatoes with fruiting vegetables and 0.91 (95% CI: 0.77, 1.07) for replacement of potatoes with other root vegetables. A higher intake of cabbage replacing other vegetable subgroups was associated with a statistically non-significant higher risk of MI. A similar pattern of associations was found when intake was expressed in kcal/week. Among men, the pattern of associations was overall found to be similar to that for women. This study supports food-based dietary guidelines recommending to consume a variety of vegetables from all subgroups.

Development and Validation of a Prognostic Nomogram Model for Recurrence of Non-Muscle Invasive Bladder Cancer

10.21203/rs.3.rs-691739/v1 ◽

2021 ◽

Author(s):

Sanhe Liu ◽

Yongzhi Li ◽

Diansheng Cui ◽

Yuexia Jiao ◽

Liqun Duan ◽

...

Keyword(s):

Bladder Cancer ◽

Risk Stratification ◽

Proportional Hazards ◽

Muscle Invasive Bladder Cancer ◽

Clinicopathologic Characteristics ◽

Muscle Invasive

Abstract BackgroundDifferent recurrence probability of non-muscle invasive bladder cancer (NMIBC) requests different adjuvant treatments and follow-up strategies. However, there is no simple, intuitive, and generally accepted clinical recurrence predictive model available for NMIBC. This study aims to construct a predictive model for the recurrence of NMIBC based on demographics and clinicopathologic characteristics from two independent centers. MethodsDemographics and clinicopathologic characteristics of 511 patients with NMIBC were retrospectively collected. Recurrence free survival (RFS) was estimated using the Kaplan-Meier method and log-rank tests. Univariate Cox proportional hazards regression analysis was used to screen variables associated with RFS, and a multivariate Cox proportional hazards regression model with a stepwise procedure was used to identify those factors of significance. A final nomogram model was built using the multivariable Cox method. The performance of the nomogram model was evaluated with respect to its calibration, discrimination, and clinical usefulness. Internal validation was assessed with bootstrap resampling. X-tile software was used for risk stratification calculated by the nomogram model. ResultsIndependent prognostic factors including tumor stage, recurrence status, and European Association of Urology (EAU) risk stratification group were introduced to the nomogram model. The model showed acceptable calibration and discrimination (area under the receiver operating characteristic [ROC] curve was 0.85; the consistency index [C-index] was 0.79 [95% CI: 0.76 to 0.82]), which was superior to the EAU risk stratification group alone. The decision curve also proved well clinical usefulness. Moreover, all populations could be stratified into three distinct risk groups by the nomogram model. ConclusionsWe established and validated a novel nomogram model that can provide individual prediction of RFS for patients with NMIBC. This intuitively prognostic nomogram model may help clinicians in postoperative treatment and follow-up decision-making.

Antibiotic and acid-suppression medications during early childhood are associated with obesity

Gut ◽

10.1136/gutjnl-2017-314971 ◽

2018 ◽

Vol 68 (1) ◽

pp. 62-69 ◽

Cited By ~ 36

Author(s):

Christopher M Stark ◽

Apryl Susi ◽

Jill Emerick ◽

Cade M Nylund

Keyword(s):

Early Childhood ◽

Department Of Defense ◽

Proportional Hazards ◽

Event Analysis ◽

Early Exposure ◽

Single Event ◽

Inclusion Criteria ◽

ObjectiveGut microbiota alterations are associated with obesity. Early exposure to medications, including acid suppressants and antibiotics, can alter gut biota and may increase the likelihood of developing obesity. We investigated the association of antibiotic, histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) prescriptions during early childhood with a diagnosis of obesity.DesignWe performed a cohort study of US Department of Defense TRICARE beneficiaries born from October 2006 to September 2013. Exposures were defined as having any dispensed prescription for antibiotic, H2RA or PPI medications in the first 2 years of life. A single event analysis of obesity was performed using Cox proportional hazards regression.Results333 353 children met inclusion criteria, with 241 502 (72.4%) children prescribed an antibiotic, 39 488 (11.8%) an H2RA and 11 089 (3.3%) a PPI. Antibiotic prescriptions were associated with obesity (HR 1.26; 95% CI 1.23 to 1.28). This association persisted regardless of antibiotic class and strengthened with each additional class of antibiotic prescribed. H2RA and PPI prescriptions were also associated with obesity, with a stronger association for each 30-day supply prescribed. The HR increased commensurately with exposure to each additional medication group prescribed.ConclusionsAntibiotics, acid suppressants and the combination of multiple medications in the first 2 years of life are associated with a diagnosis of childhood obesity. Microbiota-altering medications administered in early childhood may influence weight gain.

Testing for Covariate Effect in the Cox Proportional Hazards Regression Model

Communication in Statistics- Theory and Methods ◽

10.1080/03610920802536958 ◽

2009 ◽

Vol 38 (14) ◽

pp. 2333-2347 ◽

Cited By ~ 6

Author(s):

Karthik Devarajan ◽

Nader Ebrahimi

Keyword(s):

Regression Model ◽

Proportional Hazards ◽

Covariate Effect ◽

Identification of Arp2/3 Complex Subunits as Prognostic Biomarkers for Hepatocellular Carcinoma

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.690151 ◽

2021 ◽

Vol 8 ◽

Author(s):

Shenglan Huang ◽

Dan Li ◽

LingLing Zhuang ◽

Liying Sun ◽

Jianbing Wu

Keyword(s):

Hepatocellular Carcinoma ◽

Mrna Expression ◽

Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

Prognostic Biomarkers ◽

Migration And Invasion ◽

Regression Analyses ◽

The actin-related protein 2/3 complex (Arp2/3) is a major actin nucleator that has been widely reported and plays an important role in promoting the migration and invasion of various cancers. However, the expression patterns and prognostic values of Arp2/3 subunits in hepatocellular carcinoma (HCC) remain unclear. In this study, The Cancer Genome Atlas (TCGA) and UCSC Xena databases were used to obtain mRNA expression and the corresponding clinical information, respectively. The differential expression and Arp2/3 subunits in HCC were analyzed using the “limma” package of R 4.0.4 software. The prognostic value of each subunit was evaluated using Kaplan–Meier survival analysis and Cox proportional hazards regression analyses. The results revealed that mRNA expression of Arp2/3 members (ACTR2, ACTR3, ARPC1A, APRC1B, ARPC2, ARPC3, ARPC4, ARPC5, and ARPC5L) was upregulated in HCC. Higher expression of Arp2/3 members was significantly correlated with worse overall survival (OS) and shorter progression-free survival (PFS) in HCC patients. Cox proportional hazards regression analyses demonstrated that ACTR3, ARPC2, and ARPC5 were independent prognostic biomarkers of survival in patients with HCC. The relation between tumor immunocyte infiltration and the prognostic subunits was determined using the TIMER 2.0 platform and the GEPIA database. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanisms of prognostic subunits in the carcinogenesis of HCC. The results revealed that ACTR3, ARPC2, and ARPC5 were significantly positively correlated with the infiltration of immune cells in HCC. The GSEA results indicated that ACTR3, ARPC2, and ARPC5 are involved in multiple cancer-related pathways that promote the development of HCC. In brief, various analyses indicated that Arp2/3 complex subunits were significantly upregulated and predicted worse survival in HCC, and they found that ACTR3, ARPC2, and ARPC5 could be used as independent predictors of survival and might be applied as promising molecular targets for diagnosis and therapy of HCC in the future.

Serum FGF21 Is Associated with Future Cardiovascular Events in Patients with Coronary Artery Disease

Cardiology ◽

10.1159/000486127 ◽

2018 ◽

Vol 139 (4) ◽

pp. 212-218 ◽

Cited By ~ 9

Author(s):

Yun Shen ◽

Xueli Zhang ◽

Yiting Xu ◽

Qin Xiong ◽

Zhigang Lu ◽

...

Keyword(s):

Coronary Artery Disease ◽

Regression Analysis ◽

Coronary Artery ◽

Cardiovascular Events ◽

Proportional Hazards ◽

Kaplan Meier ◽

Artery Disease

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future.

MODELLING THE DETERMINANTS OF UNDER-FIVE CHILD MORTALITY RATES USING COX PROPORTIONAL HAZARDS REGRESSION MODEL

FUDMA Journal of Sciences ◽

10.33003/fjs-2020-0404-496 ◽

2021 ◽

Vol 4 (4) ◽

pp. 401-408

Author(s):

M. C. Musa ◽

O. E. Asiribo ◽

H. G. Dikko ◽

M. Usman ◽

S. S. Sani

Keyword(s):

Regression Model ◽

Child Mortality ◽

Proportional Hazards ◽

Mortality Rates ◽

Cox Proportional Hazards Model ◽

Predictor Variables ◽

Under Five ◽

An under-five childhood mortality rates in Nigeria is still high, despite efforts of government at all levels to combat the menace. This study examined some factors that significantly affect under-five child mortality. A sample of mothers with children under the age of five from Nigeria Demographic and Health Survey data (NDHS, 2013 & 2018) was used to assess the effect of some selected predictor variables (or covariates) on childhood survival. Cox proportional hazards model is essentially a regression model popularly used for investigating the association between the survival time and one or more predictor variables. The results from final fitted Cox proportional hazards regression model that the covariates, contraceptive used by the mother, state of residence, birth weight of child and type of toilet facility used by the h-ousehold were found to be significantly associated with under-five survival in the North Central Region of Nigeria. All the calculations are performed using the R software for statistical analysis.

Prognostic Significance of Serum Free Amino Acids in Head and Neck Cancers

Cells ◽

10.3390/cells8050428 ◽

2019 ◽

Vol 8 (5) ◽

pp. 428 ◽

Cited By ~ 3

Author(s):

Vit Vsiansky ◽

Marketa Svobodova ◽

Jaromir Gumulec ◽

Natalia Cernei ◽

Dagmar Sterbova ◽

...

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Regression Model ◽

Head And Neck ◽

Cell Lines ◽

Proportional Hazards ◽

Transformed Cells ◽

Despite distinctive advances in the field of head and neck squamous cell cancer (HNSCC) biomarker discovery, the spectrum of clinically useful prognostic serum biomarkers is limited. As metabolic activities in highly proliferative transformed cells are fundamentally different from those in non-transformed cells, specific shifts in concentration of different metabolites may serve as diagnostic or prognostic markers. Blood amino acids have been identified as promising biomarkers in different cancers before, but little is known about this field in HNSCC. Blood amino acid profiles of 140 HNSCC patients were examined using high-performance liquid chromatography. Cox proportional hazards regression model was used to assess the prognostic value of amino acid concentrations in serum. Colony forming assay was used to identify the effect of amino acids that were significant in Cox proportional hazards regression models on colony forming ability of FaDu and Detroit 562 cell lines. In the multivariable Cox regression model for overall survival (OS), palliative treatment was associated with an unfavourable prognosis while high serum levels of methionine have had a positive prognostic impact. In the relapse-free survival (RFS) multivariable model, methionine was similarly identified as a positive prognostic factor, along with tumor localization in the oropharynx. Oral cavity localization and primary radio(chemo)therapy treatment strategy have been linked to poorer RFS. 1mM serine was shown to support the forming of colonies in both tested HNSCC cell lines. Effect of methionine was exactly the opposite.