Candidate markers

Bieche, I., Parfait, B., Doussal, V. L., Olivi, M., Rio, M.-C., Lidereau, R., and Viduad, M. 2001. Identification of CGA as a novel estrogen receptor-responsive gene in breast cancer An outstanding candidate marker to predict the response to endocrine therapy. Cancer Res. 61 1652-1658. 

Welsh JB, Sapinoso LM, Su AI, Kern SG, Wang-Rodriguez J, Moskaluk CA, Frierson HF Jr, Hampton GM. Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 2001 61 5974-5978. 

Fluid biomarkers of AD currently provide indications of disease stage however, they are not robust predictors of disease progression or treatment response, and most are measured in CSF, which limits their applicability [114], Biomarkers of potential interest include CSF and peripheral levels of Ap42, protein tau, histamine, interleukins, and many other novel candidate markers in blood [7, 17, 32, 115-118],... 

In hypothesis-driven discovery programs, often a list of candidate markers are compiled using the current knowledge base. The list of candidates may be compiled with advanced bioinformatics data mining tools (i.e., electronic interpretation of scientific papers), which could generate candidates that represent members of a probable pathway, either as expressed genes, or proteins, or the affected metabolites. 

Zhang, J., Hanig, J. R, and De Felice, A. F. (2012). Biomarkers of endothelial cell activation Candidate markers for drug-induced vasculitis in patients or drug-induced vascular injury in animals. Vascul Pharmacol 56, 14-25. 

When injnry scores are dichotomized into positive and nonpositive, sensitivity and specificity are usually estimated and displayed in an ROC curve (Pepe, 2003). The area under the ROC curve (AUROC) is a common summary performance metric. Some advantages of this approach are that ROC curve estimation generally requires few assumptions, a plot of the ROC curve gives an easily interpreted visual display of results, and the AUROC is a global metric that does not require the specification of a threshold. Since both sensitivity and specificity can be greatly influenced by characteristics that are study specific such as severity or type of injury, it is advisable to compare candidate marker performance to that of standard markers. In rodent nephrotoxicity studies, candidate markers are commonly compared to sCr and BUN. 

As described previously, AUROC can be useful to quantify a marker s ability to discriminate between samples from animals with and without injury. However, it does not make clear the extent to which the information provided by the candidate marker overlaps with information provided by the standard markers. One way to address this question is to compare the performance of a model that contains the standard markers together with the new candidate marker to a model that contains the standard markers without the new marker. The net reclassification index (NRI) and integrated discrimination index (IDI) (Pencina et al., 2(X)8) are metrics that can be used to quantify and test the difference in performance between binary logistic regression models and thus assess the amount of information added by the new marker. 

Brettschneider, J., V. Lehmensiek, H. Mogel et al. Proteome analysis reveals candidate markers of disease progression in amyotrophic lateral sclerosis (AI.S ). Neurosci 2010 23-7. 

TABLE 3.7 Candidate Marker Genes Proposed by Sawada et al. [20] and Their Gene Products. 

An interesting and highly promising candidate marker protein for drug-specific T cells is the serine protease granzyme B expressed by cytotoxic... 

Ceccanti, M., Mancinelli, R., Sasso, G.F., Allen, J.P., Binetti, R., Mellini, A., Attilia, F., Toppo, L., and Attilia, M.L., 2005. Erythrocyte thiamine (Th) esters a major factor of the alcohol withdrawal syndrome or a candidate marker for alcoholism itself Alcohol and Alcoholism. 40 283-290. 

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