Cancer biomarker discovery: Opportunities and pitfalls in analytical methods

Abstract

Many diseases result in specific and characteristic changes in the chemical and biochemical profiles of biological fluids and tissues prior to development of clinical symptoms. These changes are often useful diagnostic and prognostic biomarkers. Identifying biomarkers that can be used for the early detection of cancer will result in more efficient treatments, reduction in suffering, and lower mortality rates. An ideal screening test should be non-invasive with high sensitivity and specificity. Proteomic and metabolomic analyses of biological samples can reveal changes in abundance levels of metabolites and proteins that when validated and confirmed through clinical trials can function as clinical tests for early detection, diagnosis, monitoring disease progression, and predicting therapeutic response. While the past decade has seen great advancements in proteomics and metabolomics research producing potential biomarkers for cancer, most of the identified biomarkers have failed to replace existing clinical tests. To become a clinically approved test, a potential biomarker should be confirmed and validated using hundreds of specimens and should be reproducible, specific, and sensitive. A search of the scientific and medical literature indicates that many studies report the discovery of potential biomarkers without proper validation and/or they do not meet the above criteria. In this manuscript, we will discuss the successes and the pitfalls of biomarker research and comment on study and experimental design, which in most cases is lacking, resulting in suboptimal biomarkers.

Validation of cofilin-1 as a biomarker in non-small cell lung cancer: application of quantitative method in a retrospective cohort

“…However, to be clinically acceptable, the biomarker should present not only sensitivity and specificity. Biomarker evaluation in tumor samples needs to be accurate, economical, easy to perform and reproducible by different technicians across different laboratories (Pepe et al 2001;Issaq et al 2011). Following the validation proposal, in this report we established a simple SQ-IHC method to detect and quantify cofilin-1 immunocontent in tumor biopsies.…”

Is sarcosine a biomarker for prostate cancer?

“…Additional errors can arise when the analysis is carried out by different laboratories or personnel using invalidated methods that result in different specificities and sensitivities and in certain cases different proteins or metabolites as biomarkers. In other cases provisional biomarkers have not been validated or confirmed [1][2][3]. As eloquently summarized by Grossman: ''The contradicting published reports likely result from studies testing different patient populations using different methodologies and applying different cutoffs for a positive test'' [4].…”

“…As Schalken [17] and others [1,2,18] correctly stated, an important study such as the discovery and validation of biomarkers require clear and validated standard operating procedure for sample selection, analysis and data interpretation. At this point one cannot unequivocally say if sarcosine is or is not a biomarker for prostate cancer because, as far as we and others [18] could determine, most of the above published studies used a validated and confirmed analytical method for the quantification of sarcosine.…”

Prognostic and Predictive Protein Biomarkers in Laryngeal Squamous Cell Carcinoma—A Systematic Review

“…This highlights some of the pitfalls of using proteomic techniques in cancer biomarker research. Firstly, identified biomarkers require validation in a larger population with reproducible results [78]. Only one study validated the identified biomarker in a separate population and the vast majority of studies had sample sizes of less than 20.…”