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

Chen, Hongda; Zucknick, Manuela; Werner, Simone; Knebel, Phillip; Brenner, Hermann

doi:10.1158/1078-0432.ccr-14-3051

Cited by 41 publications

(53 citation statements)

References 45 publications

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“…Although the 2-marker combination CEA þ anti-p53 alone cannot compete with the FIT, it appears plausible that a combination with further blood biomarkers, such as DNA methylation markers (30), miRNA markers (31), autoantibody markers (24), or protein markers (32,33) might increase the diagnostic performance sufficiently for an application in mass screening.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting

Werner

Krause

Rolny

et al. 2016

Clinical Cancer Research

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Purpose: In initial studies that included colorectal cancer patients undergoing diagnostic colonoscopy, we had identified a serum marker combination able to detect colorectal cancer with similar diagnostic performance as fecal immunochemical test (FIT). In this study, we aimed to validate the results in participants of a large colorectal cancer screening study conducted in the average-risk, asymptomatic screening population.Experimental Design: We tested serum samples from 1,200 controls, 420 advanced adenoma patients, 4 carcinoma in situ patients, and 36 colorectal cancer patients with a 5-marker blood test [carcinoembryonic antigen (CEA)þanti-p53þosteopontinþ sepraseþferritin]. The diagnostic performance of individual markers and marker combinations was assessed and compared with stool test results.Results: AUCs for the detection of colorectal cancer and advanced adenomas with the 5-marker blood test were 0.78 [95% confidence interval (CI), 0.68-0.87] and 0.56 (95% CI, 0.53-0.59), respectively, which now is comparable with guaiacbased fecal occult blood test (gFOBT) but inferior to FIT. With cutoffs yielding specificities of 80%, 90%, and 95%, the sensitivities for the detection of colorectal cancer were 64%, 50%, and 42%, and early-stage cancers were detected as well as late-stage cancers. For osteopontin, seprase, and ferritin, the diagnostic performance in the screening setting was reduced compared with previous studies in diagnostic settings while CEA and anti-p53 showed similar diagnostic performance in both settings.Conclusions: Performance of the 5-marker blood test under screening conditions is inferior to FIT even though it is still comparable with the performance of gFOBT. CEA and anti-p53 could contribute to the development of a multiple marker blood-based test for early detection of colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting

Werner

Krause

Rolny

et al. 2016

Clinical Cancer Research

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“…Early diagnosis and prompt treatment substantially improve outcome in CRC patients (2). At present, studies are being conducted in order to identify biological substances that may be involved in cancer development (3). The identification of specific cancer biomarkers is expected to improve early cancer diagnosis in the asymptomatic stage of the disease (4).…”

Section: Introductionmentioning

confidence: 99%

Colorectal cancer patients exhibit increased levels of galanin in serum and colon tissues

et al. 2016

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Galanin (GAL) is a 30-amino acid neuropeptide that is expressed in both the central and peripheral nervous system, including the enteric nervous system (ENS). Increased GAL concentrations have been identified in the blood of colorectal cancer (CRC) patients. The aim of the present study was to assess whether sections of the colon wall containing ENS plexuses or CRC tumor are associated with increased GAL concentrations. Blood samples were collected from 68 CRC patients and 39 healthy volunteers. In addition, samples of CRC tumors and colon wall tissue in close proximity to and distant from the neoplastic tissue were obtained from 22 CRC patients. The GAL concentration of sera and tissue homogenates obtained from three sections of the colon wall (mucosa with submucosa, muscularis externa and CRC tumor) was analyzed by ELISA. The localization of GAL was evaluated using immunohistochemistry and morphometry was used to measure the distribution of GAL-immunoreactive (GAL-Ir) myenteric plexuses in the vicinity of cancer invasion and in sections of the colon wall distant from the tumor. The GAL serum concentration of CRC patients was 2.4 times higher than that of the control group. The GAL concentration was highest in the homogenates of neoplastic tissue and mucosa obtained from the control (distant) section of the intestinal wall, followed by that in the mucosa and muscularis externa proximal to the tumor. The lowest GAL concentrations were identified within the muscular layer of the colon wall located distant from the tumor. Strong GAL immunoreactivity was identified in the cancer cells, intestinal epithelium and the submucosal and myenteric plexuses. Morphometric analysis revealed that the GAL-Ir myenteric plexuses in the vicinity of tumor infiltration were significantly smaller in size than those in the intact section of the large intestine. Furthermore, no associations were identified between the clinicopathological characteristics of CRC patients and GAL serum and tissue concentration. The increased GAL serum concentrations observed in CRC patients in comparison to healthy controls may result from GAL secretion by CRC tumors, however, other sources of GAL cannot be excluded. The atrophy of myenteric plexuses within close proximity to the tumor may affect the colon function of CRC patients. In conclusion, investigation into the presence of GAL in the colon wall and serum of CRC patients revealed that serum and tissue GAL levels may present useful potential biomarkers in CRC patients.

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“…PEA is a 96-plex immunoassay that allows high throughput detection of protein biomarkers in liquid samples 4 . 1µl of plasma sample was used from each patient to identify a pre-selected panel of 92 human proteins (full list in the supplementary appendix).…”

mentioning

confidence: 99%

Proteomic profiling in plasma cell disorders: a feasibility study

Mailankody

Devlin

Korde

et al. 2016

Leukemia & Lymphoma

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

Cited by 41 publications

References 45 publications

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting

Evaluation of a 5-Marker Blood Test for Colorectal Cancer Early Detection in a Colorectal Cancer Screening Setting

Colorectal cancer patients exhibit increased levels of galanin in serum and colon tissues

Proteomic profiling in plasma cell disorders: a feasibility study

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