Increased Plasma Levels of the APC-Interacting Protein MAPRE1, LRG1, and IGFBP2 Preceding a Diagnosis of Colorectal Cancer in Women

Abstract

Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease prior to clinical diagnosis. We investigated plasma samples from the Women’s Health Initiative (WHI) cohort to determine quantitative differences in plasma proteins between subjects subsequently diagnosed with colorectal cancer (CRC) and matched controls that remained cancer free during the period of follow-up. Proteomic analysis of WHI samples collected prior to diagnosis of CRC resulted in the identification of six proteins with significantly (p <0.05) elevated concentrations in cases compared to controls. Proteomic analysis of two colorectal cancer cell lines showed 5 of the 6 proteins were produced by cancer cells. MAPRE1, IGFBP2, LRG1 and CEA were individually assayed by enzyme linked immunosorbent assay (ELISA) in 58 pairs of newly diagnosed CRC samples and controls and yielded significant elevations (p <0.05) among cases relative to controls. A combination of these four markers resulted in an ROC with an AUC=0.841 and 57% sensitivity at 95% specificity. This combination rule was tested in an independent set of WHI samples collected within 7 months prior to diagnosis from cases and matched controls resulting in 41% sensitivity at 95% specificity. A panel consisting of CEA, MAPRE1, IGFBP2 and LRG1 has predictive value in pre-diagnostic colorectal cancer plasmas.

Head-to-Head Comparison and Evaluation of 92 Plasma Protein Biomarkers for Early Detection of Colorectal Cancer in a True Screening Setting

“…In our analyses, CEA was found to have higher plasma levels in colorectal cancer patients at advanced stages compared with early ones, which is consistent with previous evidence (39). Nevertheless, although CEA is limited by its poor diagnostic efficacy as a single biomarker, it could still be used in a multimarker panel to enhance the diagnostic performance, which was also seen in other studies (40,41).…”

Sequential Validation of Blood-Based Protein Biomarker Candidates for Early-Stage Pancreatic Cancer

“…A role for LRG1 has been suggested in promoting angiogenesis through activation of the TGF-b pathway (40). Apart from PDAC, increased LRG1 plasma levels have also been found in other cancer types (41)(42)(43)(44)(45).…”

LRG1 modulates invasion and migration of glioma cell lines through TGF-β signaling pathway

“…Studies have shown that the level of LRG1 is elevated in the sera and the tumor tissues of patients with non-small-cell lung cancer (Nakajima et al, 2011;O'Donnell et al, 2002). Similarly, the level of LRG1 has been found to be elevated in the sera of colorectal cancer patients, and is closely correlated with tumor progression (Ladd et al, 2012). Recently, Nakajima et al (2012) showed that LRG1 is distributed throughout the entire brain and is mainly expressed in the astrocytes with the expression increasing with age, suggesting a possibility of the involvement of LRG1 in astrocytic malignancy and glioma tumorigenesis.…”