Improved Diagnosis of Colorectal Cancer Using a Combination of Fecal Occult Blood and Novel Fecal Protein Markers

Karl, J. Philip; Wild, Norbert; Tacke, Michael; Andres, Herbert; Garczarek, Ursula; Rollinger, Wolfgang; Zolg, Werner

doi:10.1016/j.cgh.2008.04.021

Cited by 61 publications

(55 citation statements)

References 27 publications

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“…Blood and stool samples were collected prospectively in 2 European multicenter studies that have previously been described (13). The respective research protocols were reviewed and approved by the appropriate ethics committees and written informed consent was obtained from patients prior to sample collection.…”

Section: Study Design and Sample Collectionmentioning

confidence: 99%

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A Combination of Serum Markers for the Early Detection of Colorectal Cancer

Wild

Andres

Rollinger

et al. 2010

Clinical Cancer Research

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Purpose: Fecal occult blood testing is recommended as first-line screening to detect colorectal cancer (CRC). We evaluated markers and marker combinations in serum as an alternative to improve the detection of CRC.Experimental Design: Using penalized logistic regression, 6 markers were selected for evaluation in 1,027 samples (301 CRC patients, 143 patients with adenoma, 266 controls, 141 disease controls, and 176 patients with other cancer). The diagnostic performance of each marker and of marker combinations was assessed.Results: To detect CRC from serum samples, we tested 22 biomarkers. Six markers were selected for a marker combination, including the known tumor markers CEA (carcinoembryonic antigen) and CYFRA 21-1 as well as novel markers or markers that are less routinely used for the detection of CRC: ferritin, osteopontin (OPN), anti-p53, and seprase. CEA showed the best sensitivity at 95% specificity with 43.9%, followed by seprase (42.4%), CYFRA 21-1 (35.5%), OPN (30.2%), ferritin (23.9%), and anti-p53 (20.0%). A combination of these markers gave 69.6% sensitivity at 95% specificity and 58.7% at 98% specificity. Focusing on International Union against Cancer (UICC) stages 0-III reduced the sensitivity slightly to 68.0% and 53.3%, respectively. In a subcollective, with matched stool samples (75 CRC cases and 234 controls), the sensitivity of the marker combination was comparable with fecal immunochemical testing (FIT) with 82.4% and 68.9% versus 81.8% and 72.7% at 95% and 98% specificity, respectively.Conclusions: The performance of the serum marker combination is comparable with FIT. This provides a novel tool for CRC screening to trigger a follow-up colonoscopy for a final diagnosis. Clin Cancer Res; 16(24); 6111-21. Ó2010 AACR.The early detection of colorectal cancer (CRC) significantly improves the prognosis of patients and is a key factor to reduce the mortality from CRC (1). Recently, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology have issued joint guidelines for CRC screening to include well-known procedures as guaiac-based fecal occult blood testing (FOBT) and fecal immunochemical testing (FIT), colonoscopy, sigmoidoscopy, and double-contrast barium enema, but also 2 more recent methods, computer tomography colonography and fecal DNA testing (2). The guidelines of the U.S. Preventive Services Task Force have also been updated but do not include the latter 2 methods (3).Serum-based, minimally invasive markers would be highly attractive for CRC screening as they could easily be integrated in any health checkup without the need of additional stool sampling. Although numerous biomarkers are under evaluation for the detection of CRC from serum, none of them has sufficient sensitivity and specificity to be considered in the current guidelines (4). Carcinoembryonic antigen (CEA) and carbohydrate antigens, for example, CA19-9 have been assessed more intensely but with varying results depending on the study design and the s...

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Section: Study Design and Sample Collectionmentioning

confidence: 99%

“…The assay was calibrated using a highly positive serum with 1,000 U/mL corresponding to an optical density of 3.0 at 450 nm. Fecal assays, hemoglobin-haptoglobin (Hb-Hpt) complex, and S100A12, were conducted as reported (13).…”

Section: Translational Relevancementioning

confidence: 99%

A Combination of Serum Markers for the Early Detection of Colorectal Cancer

Wild

Andres

Rollinger

et al. 2010

Clinical Cancer Research

Self Cite

121

110

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“…While most controls were recruited in a screening setting, colorectal cancer cases recruited from surgery centers were used to enrich the number of cancer cases due to the low prevalence of colorectal cancer in the screening population (10,11). A multivariate analysis of 60 candidate biomarkers identified a 6-marker panel consisting of CEA, ferritin, seprase, osteopontin, anti-p53 autoantibody, and CYFRA-21-1.…”

Section: Introductionmentioning

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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“…The fecal occult blood test (FOBT) is a simple and non-invasive test that has been shown to decrease mortality rates associated with CRC (27). However, it was reported that a positive FOBT result was observed in less than 10% of the patients with CRC (28 (30). They showed that the sensitivity of fecal TIMP-1 was 72%; however, its combination with S100A12 and hemoglobin-haptoglobin had 95% specificity and 88% sensitivity.…”

Section: Discussionmentioning

confidence: 99%

The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

Kiyak

Keles

Bengi

et al. 2018

J Basic Clin Health Sci

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Purpose: Colorectal cancer (CRC) is one of the most common and death related cancers in the world. Therefore, the early diagnosis of CRC remains with a great importance to prevent its further progression and increase survival rates. Colonoscopy and pathological examinations which are invasive and painful procedures, are needed to make a definitive diagnosis of CRC. The carcinoembryonic antigen (CEA) is particularly used for postoperative follow-up of CRC patients. The imbalance between matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) leads to degradation of extracellular matrix which is the most important step in invasion and metastasis. It was also observed that cyclooxygenase-2 (COX-2) has crucial roles in the development and progression of colorectal cancer. The purpose of our study is to detect fecal and plasma MMP-7, COX-2, TIMP-1, and CEA protein levels in patients with colorectal cancer, colorectal polyps, and healthy individuals, and assess their association with each other and with clinicopathological variables. We also aimed to evaluate plasma and fecal MMP-7, COX-2, TIMP-1, and CEA protein levels as potential diagnostic markers in colorectal carcinoma.Methods: Plasma and fecal samples were taken from patients with fifteen colorectal cancers, twenty-six colorectal polyps, and thirty-three healthy volunteers. Protein extraction was carried out from fecal samples. Plasma and fecal MMP-7, TIMP-1, and COX-2 protein levels were determined by ELISA whereas plasma and fecal CEA protein levels were detected with CEIA.Results: Plasma and fecal CEA levels were significantly higher in CRC than the control. In addition, plasma TIMP-1 and plasma CEA levels were significantly elevated in cancer according to polyp group. We also detected decreased plasma MMP-7 levels in polyps compared to control group. Positive correlations were observed among plasma COX-2 and TIMP-1 levels (r=0.571), fecal COX-2 and CEA levels (r=0.764) in CRC. However, no association was found between biochemical parameters and clinicopathological variables. ROC analysis for discriminating CRC from healthy controls showed that area under curves (AUC) for fecal and plasma CEA levels were 0.763 and 0.692, respectively. Plasma CEA (AUC=0.735), plasma TIMP-1 (AUC=0.706), and their combination (AUC=0.760) exhibited significant diagnostic performances to differentiate CRC from polyp. In discrimination colorectal polyps from healthy tissues, MMP-7 showed the highest AUC value (0.667). Conclusion:Here we suggested that plasma and fecal CEA protein levels may be potential predictive noninvasive markers for diagnosis of colorectal adenocarcinoma. In addition, plasma CEA and TIMP-1 are also valuable biomarker candidates in differentiating colorectal cancer from colorectal polyps.

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Improved Diagnosis of Colorectal Cancer Using a Combination of Fecal Occult Blood and Novel Fecal Protein Markers

Cited by 61 publications

References 27 publications

A Combination of Serum Markers for the Early Detection of Colorectal Cancer

A Combination of Serum Markers for the Early Detection of Colorectal Cancer

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

The Importance of Fecal and Plasma CEA, COX-2, MMP-7, and TIMP-1 in the Diagnosis of Colorectal Cancer

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