Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women - PubMed (original) (raw)

doi: 10.1158/1940-6207.CAPR-11-0412. Epub 2012 Jan 25.

Tina Busald, Melissa M Johnson, Qing Zhang, Sharon J Pitteri, Hong Wang, Dean E Brenner, Paul D Lampe, Raju Kucherlapati, Ziding Feng, Ross L Prentice, Samir M Hanash

Affiliations

Increased plasma levels of the APC-interacting protein MAPRE1, LRG1, and IGFBP2 preceding a diagnosis of colorectal cancer in women

Jon J Ladd et al. Cancer Prev Res (Phila). 2012 Apr.

Abstract

Longitudinal blood collections from cohort studies provide the means to search for proteins associated with disease before 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 before diagnosis of CRC resulted in the identification of six proteins with significantly (P < 0.05) elevated concentrations in cases compared with controls. Proteomic analysis of two CRC cell lines showed that five of the six proteins were produced by cancer cells. Microtubule-associated protein RP/EB family member 1 (MAPRE1), insulin-like growth factor-binding protein 2 (IGFBP2), leucine-rich alpha-2-glycoprotein (LRG1), and carcinoembryonic antigen (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 a receiver operating characteristics curve with an area under the curve value of 0.841 and 57% sensitivity at 95% specificity. This combination rule was tested in an independent set of WHI samples collected within 7 months before 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 prediagnostic CRC plasmas.

2012 AACR

PubMed Disclaimer

Figures

Figure 1

Figure 1

Tryptic peptides identified from MS experiments for IPAS experiments for a) MAPRE1, b) LRG1, c) IGFBP2, d) ENO1, e) ARMET and f) PDIA3. Each line represents peptides identified or quantified in an individual IPAS. The top line in each figure represents theoretical peptides generated by tryptic digestion. Blue peptides indicate non-cysteine containing tryptic peptides, while red peptides are cysteine-containing tryptic peptides that could be quantified from the acrylamide labeling. In the experimental data, blue peptides indicate the peptide was identified, but not quantified, while red peptides indicate the peptide had quantification data from the acrylamide labeling.

Figure 1

Figure 1

Tryptic peptides identified from MS experiments for IPAS experiments for a) MAPRE1, b) LRG1, c) IGFBP2, d) ENO1, e) ARMET and f) PDIA3. Each line represents peptides identified or quantified in an individual IPAS. The top line in each figure represents theoretical peptides generated by tryptic digestion. Blue peptides indicate non-cysteine containing tryptic peptides, while red peptides are cysteine-containing tryptic peptides that could be quantified from the acrylamide labeling. In the experimental data, blue peptides indicate the peptide was identified, but not quantified, while red peptides indicate the peptide had quantification data from the acrylamide labeling.

Figure 1

Figure 1

Tryptic peptides identified from MS experiments for IPAS experiments for a) MAPRE1, b) LRG1, c) IGFBP2, d) ENO1, e) ARMET and f) PDIA3. Each line represents peptides identified or quantified in an individual IPAS. The top line in each figure represents theoretical peptides generated by tryptic digestion. Blue peptides indicate non-cysteine containing tryptic peptides, while red peptides are cysteine-containing tryptic peptides that could be quantified from the acrylamide labeling. In the experimental data, blue peptides indicate the peptide was identified, but not quantified, while red peptides indicate the peptide had quantification data from the acrylamide labeling.

Figure 1

Figure 1

Tryptic peptides identified from MS experiments for IPAS experiments for a) MAPRE1, b) LRG1, c) IGFBP2, d) ENO1, e) ARMET and f) PDIA3. Each line represents peptides identified or quantified in an individual IPAS. The top line in each figure represents theoretical peptides generated by tryptic digestion. Blue peptides indicate non-cysteine containing tryptic peptides, while red peptides are cysteine-containing tryptic peptides that could be quantified from the acrylamide labeling. In the experimental data, blue peptides indicate the peptide was identified, but not quantified, while red peptides indicate the peptide had quantification data from the acrylamide labeling.

Figure 1

Figure 1

Tryptic peptides identified from MS experiments for IPAS experiments for a) MAPRE1, b) LRG1, c) IGFBP2, d) ENO1, e) ARMET and f) PDIA3. Each line represents peptides identified or quantified in an individual IPAS. The top line in each figure represents theoretical peptides generated by tryptic digestion. Blue peptides indicate non-cysteine containing tryptic peptides, while red peptides are cysteine-containing tryptic peptides that could be quantified from the acrylamide labeling. In the experimental data, blue peptides indicate the peptide was identified, but not quantified, while red peptides indicate the peptide had quantification data from the acrylamide labeling.

Figure 1

Figure 1

Tryptic peptides identified from MS experiments for IPAS experiments for a) MAPRE1, b) LRG1, c) IGFBP2, d) ENO1, e) ARMET and f) PDIA3. Each line represents peptides identified or quantified in an individual IPAS. The top line in each figure represents theoretical peptides generated by tryptic digestion. Blue peptides indicate non-cysteine containing tryptic peptides, while red peptides are cysteine-containing tryptic peptides that could be quantified from the acrylamide labeling. In the experimental data, blue peptides indicate the peptide was identified, but not quantified, while red peptides indicate the peptide had quantification data from the acrylamide labeling.

Figure 2

Figure 2

ELISA results in newly diagnosed samples of a) CEA, b) MAPRE1, c) LRG1, d) IGFBP2. Each circle represents one of 58 individual cases or matched controls. **** indicates p<0.0001 based on paired Wilcox test.

Figure 2

Figure 2

ELISA results in newly diagnosed samples of a) CEA, b) MAPRE1, c) LRG1, d) IGFBP2. Each circle represents one of 58 individual cases or matched controls. **** indicates p<0.0001 based on paired Wilcox test.

Figure 2

Figure 2

ELISA results in newly diagnosed samples of a) CEA, b) MAPRE1, c) LRG1, d) IGFBP2. Each circle represents one of 58 individual cases or matched controls. **** indicates p<0.0001 based on paired Wilcox test.

Figure 2

Figure 2

ELISA results in newly diagnosed samples of a) CEA, b) MAPRE1, c) LRG1, d) IGFBP2. Each circle represents one of 58 individual cases or matched controls. **** indicates p<0.0001 based on paired Wilcox test.

Figure 3

Figure 3

a) ROC analysis of a linear combination of the four markers from a) compared to CEA in newly diagnosed samples. b) ROC analysis of the same linear combination of the four markers in a) compared to CEA in pre-diagnostic samples. Coefficients for combination of the four markers are: CEA: 3.612e-2; IGFBP2: 7.052e-3; LRG1: 7.263e-5; MAPRE1: 2.766e-2.

Figure 3

Figure 3

a) ROC analysis of a linear combination of the four markers from a) compared to CEA in newly diagnosed samples. b) ROC analysis of the same linear combination of the four markers in a) compared to CEA in pre-diagnostic samples. Coefficients for combination of the four markers are: CEA: 3.612e-2; IGFBP2: 7.052e-3; LRG1: 7.263e-5; MAPRE1: 2.766e-2.

References

    1. Hawk ET, Levin B. Colorectal cancer prevention. Journal of Clinical Oncology. 2005;23:378–91. - PubMed
    1. Singh H, Turner D, Xue L, Targownik LE, Bernstein CN. Risk of developing colorectal cancer following a negative colonoscopy examination - Evidence for a 10-year interval between colonoscopies. Jama-Journal of the American Medical Association. 2006;295:2366–73. - PubMed
    1. Seeff LC, Manninen DL, Dong FB, Chattopadhyay SK, Nadel MR, Tangka FKL, et al. Is there endoscopic capacity to provide colorectal cancer screening to the unscreened population in the United States? Gastroenterology. 2004;127:1661–9. - PubMed
    1. Wee CC, McCarthy EP, Phillips RS. Factors associated with colon cancer screening: the role of patient factors and physician counseling. Preventive Medicine. 2005;41:23–9. - PubMed
    1. Denberg TD, Melhado TV, Coombes JM, Beaty BL, Berman K, Byers TE, et al. Predictors of nonadherence to screening colonoscopy. Journal of General Internal Medicine. 2005;20:989–95. - PMC - PubMed

MeSH terms

Substances

LinkOut - more resources