Blood-Based Protein Biomarker Panel for the Detection of Colorectal Cancer

Abstract

BackgroundThe majority of colorectal cancer (CRC) cases are preventable by early detection and removal of precancerous polyps. Even though CRC is the second most common internal cancer in Australia, only 30 per cent of the population considered to have risk factors participate in stool-based test screening programs. Evidence indicates a robust, blood-based, diagnostic assay would increase screening compliance. A number of potential diagnostic blood-based protein biomarkers for CRC have been reported, but all lack sensitivity or specificity for use as a stand-alone diagnostic. The aim of this study was to identify and validate a panel of protein-based biomarkers in independent cohorts that could be translated to a reliable, non-invasive blood-based screening test.Principal FindingsIn two independent cohorts (n = 145 and n = 197), we evaluated seven single biomarkers in serum of CRC patients and age/gender matched controls that showed a significant difference between controls and CRC, but individually lack the sensitivity for diagnostic application. Using logistic regression strategies, we identified a panel of three biomarkers that discriminated between controls and CRC with 73% sensitivity at 95% specificity, when applied to either of the two cohorts. This panel comprised of Insulin like growth factor binding protein 2 (IGFBP2), Dickkopf-3 (DKK3), and Pyruvate kinase M2(PKM2).ConclusionsDue to the heterogeneous nature of CRC, a single biomarker is unlikely to have sufficient sensitivity or specificity for use as a stand-alone diagnostic screening test and a panel of markers may be more effective. We have identified a 3 biomarker panel that has higher sensitivity and specificity for early stage (Stage I and -II) disease than the faecal occult blood test, raising the possibility for its use as a non-invasive blood diagnostic or screening test.

Systematic review of blood diagnostic markers in colorectal cancer

“…The study showed a sensitivity of 73% and specificity of 95% in detecting CRC [23]. The sensitivity of detecting early stage cancer was moderate with 59% in stage I and 84% in stage II.…”

Differential gene expression analysis reveals novel genes and pathways in pediatric septic shock patients

“…Multi-omics sequencing technologies have increased the number of genetic biomarkers 2 . Single or combination biomarkers are increasingly being analyzed and tested in the context of genes, RNA, or proteins [3][4][5][6] . Many strategies for uncovering biomarkers exist, such as mass-spectrometry-based, protein arrays and gene-expression profiling.…”

Electrochemistry-based approaches to low cost, high sensitivity, automated, multiplexed protein immunoassays for cancer diagnostics

“…However, inclusion of a specific set of biomarkers in the panel will be crucial. 12,13 For example, Levels of PSA in normal subjects range between 0.5 – 2 ng/mL and 4 – 10 ng/mL for cancer patients while for IL-6 normal levels are <7 pg/mL and for cancer patients up to 5 ng/mL, respectively. Given this situation, we need to develop approaches such that these biomarkers can be placed together on a single detection assay.…”