Subscribe to Newsletter
Fields & Applications Liquid Chromatography, Mass Spectrometry, Data Analysis, Proteomics

Bridging the Biomarker Gap

Biomarker discovery and validation relies heavily on reproducible and robust analytical methodology. Separation science and notably high performance liquid chromatography (HPLC) are essential and efforts spent in developing more efficient and robust HPLC stationary phases, together with advanced mass spectrometers, have made modern biomarker research possible. Given that many clinical biomarkers are proteins, advances in protein bioanalysis and proteomics have also been critical in driving the biomarker field forward. Many new biomarker candidates are proposed for various diseases every week – but often from small-scale studies lacking statistical power.

Rather disappointingly, only a few biomarker candidates survive the validation phase...

Sorting through this mountain of information and prioritizing biomarkers for further validation is a challenge. And rather disappointingly, only a few biomarker candidates survive the validation phase in large clinical studies – even fewer enter commercial development and clinical application. This “biomarker gap” is recognized and major efforts are being deployed to professionalize biomarker discovery and validation. The recently founded Dutch Biomarker Development Center, a public-private partnership consortium, is a good example of the actions taken  (

I will talk about the challenges inherent to any biomarker discovery and development program with a focus on analytical science at HPLC 2015 in Geneva. I shall highlight pre-analytical factors that may bias biomarker studies, leading to discoveries that cannot be validated later on. I will exemplify this with studies on cervical cancer (1) and multiple sclerosis (2), and refer to other published studies where appropriate. While HPLC coupled to mass spectrometry holds great promise to gain a better understanding of the intricate changes that occur in protein and metabolite profiles in body fluids or tissue, it is vital that researchers are aware of the need for equally powerful data processing and statistical analysis approaches.

I’ll also highlight some examples showing that data processing and statistical analysis alone may influence the final result considerably (3). I have no doubt that the trio comprising well-designed comparative clinical studies addressing relevant disease-related questions, validated and robust analytical techniques, and reliable data processing and analysis forms the basis for successful biomarker research. Notwithstanding some setbacks, the field is alive and still holds great promise notably in the field of personalized medicine.

See you at HPLC 2015 in Geneva (

Receive content, products, events as well as relevant industry updates from The Analytical Scientist and its sponsors.
Stay up to date with our other newsletters and sponsors information, tailored specifically to the fields you are interested in

When you click “Subscribe” we will email you a link, which you must click to verify the email address above and activate your subscription. If you do not receive this email, please contact us at [email protected].
If you wish to unsubscribe, you can update your preferences at any point.

  1. A. P. Boichenko et al., “A Panel of Regulated Proteins in Serum from Patients with Cervical Intraepithelial Neoplasia and Cervical Cancer”, J. of Proteome Res. 13, 4995-5007 (2014).
  2. T. Rosenling et al., “The Impact of Delayed Storage on the Measured Proteome and Metabolome of Human Cerebrospinal Fluid”, Clinical Chemistry 57, 1703-1711 (2011).
  3. T. Rosenling et al., “The Effect of Pre-Analytical Factors on Stability of the Proteome and Selected Metabolites in Cerebrospinal Fluid (CSF)”, J. Proteome Res. 8, 5511-5522 (2009).
About the Author
Rainer Bischoff

In 1987, Rainer Bischoff joined Transgene (Strasbourg, France) where he began protein-related research. He pioneered the application of mass spectrometry to characterizing recombinant proteins and published one of the first papers on this technique in 1990. Rainer continued his industrial career at AstraZeneca R&D (Lund, Sweden) before joining the Faculty of Mathematics and Natural Sciences at the University of Groningen (The Netherlands) in 2001, where he is full professor of Analytical Biochemistry. His research interests focus on biomarker discovery and validation, bioinformatics, the bioanalysis of biopharmaceutical proteins and the development of novel instrumental analytical techniques. He is the author of more than 160 peer-reviewed publications and book chapters and holds 12 patents.

Related Application Notes
Reproducible oligonucleotide IEX analyses from the very first injection!

| Contributed by YMC

Separation of plasmid isoforms using BioPro HIC BF

| Contributed by YMC

Safer AAV Analysis with Non-toxic AEX Method

| Contributed by Tosoh

Related Product Profiles
The fine Art of Method Development

| Contributed by Shimadzu Europa

Higher Peaks – Clearly.

| Contributed by Shimadzu Europa

Compact with countless benefits

| Contributed by Shimadzu Europa

Register to The Analytical Scientist

Register to access our FREE online portfolio, request the magazine in print and manage your preferences.

You will benefit from:
  • Unlimited access to ALL articles
  • News, interviews & opinions from leading industry experts
  • Receive print (and PDF) copies of The Analytical Scientist magazine