The Effect of Ignoring Statistical Interactions in Regression Analyses Conducted in Epidemiologic Studies: An Example with Survival Analysis Using Cox Proportional Hazards Regression Model

Oral squamous cell carcinoma (OSCC) is a major malignant cancer of the head and neck. Long non-coding RNAs (lncRNAs) have emerged as critical regulators during the development and progression of cancers. This study aimed to identify a lncRNA-related signature with prognostic value for evaluating survival outcomes and to explore the underlying molecular mechanisms of OSCC. Associations between overall survival (OS), disease-free survival (DFS) and candidate lncRNAs were evaluated by Kaplan–Meier survival analysis and univariate and multivariate Cox proportional hazards regression analyses. The robustness of the prognostic significance was shown via the Gene Expression Omnibus (GEO) database. A total of 2,493 lncRNAs were differentially expressed between OSCC and control samples (fold change >2, p < 0.05). We used Kaplan–Meier survival analysis to identify 21 lncRNAs for which the expression levels were associated with OS and DFS of OSCC patients (p < 0.05) and found that down-expression of lncRNA AC012456.4 especially contributed to poor DFS (p = 0.00828) and OS (p = 0.00987). Furthermore, decreased expression of AC012456.4 was identified as an independent prognostic risk factor through multivariate Cox proportional hazards regression analyses (DFS: p = 0.004, hazard ratio (HR) = 0.600, 95% confidence interval(CI) [0.423–0.851]; OS: p = 0.002, HR = 0.672, 95% CI [0.523–0.863). Gene Set Enrichment Analysis (GSEA) indicated that lncRNA AC012456.4 were significantly enriched in critical biological functions and pathways and was correlated with tumorigenesis, such as regulation of cell activation, and the JAK-STAT and MAPK signal pathway. Overall, these findings were the first to evidence that AC012456.4 may be an important novel molecular target with great clinical value as a diagnostic, therapeutic and prognostic biomarker for OSCC patients.

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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 ◽

Cox Proportional Hazards ◽

Covariate Effect ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression

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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 ◽

Cox Proportional Hazards ◽

Gene Set Enrichment Analysis ◽

Prognostic Biomarkers ◽

Migration And Invasion ◽

Regression Analyses ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression

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.

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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 ◽

Cox Proportional Hazards Model ◽

Predictor Variables ◽

Under Five ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression

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.

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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 ◽

Cox Proportional Hazards ◽

Transformed Cells ◽

Cox Proportional Hazards Regression ◽

Proportional Hazards Regression

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.

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