Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor M2-PK

Tonus, Carolin

doi:10.3748/wjg.v12.i43.7007

Cited by 57 publications

(58 citation statements)

References 27 publications

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“…The finding that faecal tumour M2 PK levels are not markedly increased in subjects with colorectal adenomas is in contrast to the much higher overall sensitivity that has been reported for invasive CRC, but it is consistent with the stage-dependent performance of this test observed for CRC: all pertinent studies reported notably higher sensitivity for more advanced CRC than for less advanced CRC (Hardt et al, 2004;Tonus et al, 2006;Haug et al, 2007;Mulder et al, 2007;Koss et al, 2008). This suggests that in the precancerous phase, the critical stage of neoplasia leading to increased faecal tumour M2 PK levels may not be reached yet.…”

Section: Discussionsupporting

confidence: 79%

“…Previous studies investigating this test reported a comparably high sensitivity for CRC ranging about 70 -80%, whereas specificity ranged about 70 -90% (Hardt et al, 2004;Vogel et al, 2005;Shastri et al, 2006;Tonus et al, 2006;Haug et al, 2007;Mulder et al, 2007;Koss et al, 2008). However, the potential of the tumour M2 PK test to detect colorectal adenomas, an issue that is highly relevant for estimating its use in reducing CRC incidence and mortality, has been investigated rarely and with rather limited sample size only (Vogel et al, 2005;Shastri et al, 2006;Mulder et al, 2007;Koss et al, 2008).…”

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confidence: 99%

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Sensitivity and specificity of faecal tumour M2 pyruvate kinase for detection of colorectal adenomas in a large screening study

2008

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The measurement of faecal tumour M2 pyruvate kinase (tumour M2 PK) has been proposed as a novel approach for early detection of colorectal cancer (CRC). However, as regards the potential of the test to detect precursors to CRC, an issue that is highly relevant to estimate its use in reducing CRC incidence and mortality, the available evidence is scant and controversial. The aim of our study was to determine the performance characteristics of the tumour M2 PK test with respect to colorectal adenomas in the target population of screening. Among 1082 participants of screening colonoscopy in Germany, of whom 30% had any adenoma and 10% had an advanced adenoma, the median (interquartile range) tumour M2 PK level in the whole study population was 1.3 U ml À1 (0.3 -3.3). At a cutoff value of 4 U ml À1 , sensitivity was 22 and 23% for detection of advanced and other adenomas, respectively, whereas specificity was 82%. The area under the receiver-operating characteristics curve (95% confidence interval) was 0.54 (0.51 -0.58) and 0.56 (0.52 -0.59) for advanced and other adenomas, respectively. In conclusion, the tumour M2 PK test has only very limited potential to distinguish between people bearing precursors to CRC and people with no finding at colonoscopy.

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Section: Discussionsupporting

confidence: 79%

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confidence: 99%

Sensitivity and specificity of faecal tumour M2 pyruvate kinase for detection of colorectal adenomas in a large screening study

2008

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“…In 2010, a meta-analysis reported a sensitivity (67%) and specificity (8 %) for immunological FOBt compared with 54% and 80% for g-FOBt, for the detection of colorectal cancer and pre-cancerous neoplasia [7]. The low sensitivity of g-FOBt has led to criticism of its use for population-based screening [9].…”

Section: Introductionmentioning

confidence: 99%

“…An alternative faecal-based screening tool is tumour M2-pyruvate kinase (tM2-PK) [9,10]. tM2-PK is an isoenzyme of pyruvate kinase; it is involved in glycolysis and catalyzes the ATP-producing conversion of phosphoenolpyruvate to pyruvate.…”

Section: Introductionmentioning

confidence: 99%

“…Abundance of tM2-PK can be quantified by a sandwich enzyme-linked immunosorbent assay (ELISA, ScheBo Biotech AG, Giessen, Germany). A number of studies have demonstrated increased abundance of plasma tM2-PK and correlation with stage of melanoma, thyroid, breast, lung, kidney, oesophageal, gastric, pancreatic, colorectal, ovarian, cervical and renal cell cancer [9,13,14]. Increased plasma concentration of tM2-PK has also been described in other colonic pathology, including diverticulosis and inflammatory bowel disease.…”

Section: Introductionmentioning

confidence: 99%

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Correlation between Faecal Tumour M2 Pyruvate Kinase and Colonoscopy for the Detection of Adenomatous Neoplasia in a Secondary Care Cohort

Bond

Burkitt

Sawbridge

et al. 2016

JGLD

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Background & Aims: Colorectal cancer screening programmes that target detection and excision of adenomatous colonic polyps have been shown to reduce colorectal cancer related mortality. Many screening programmes include an initial faecal occult blood test (FOBt) prior to colonoscopy. To refine the selection of patients for colonoscopy other faecal-based diagnostic tools have been proposed, including tumour M2-pyruvate kinase (tM2-PK). To determine whether tM2-PK quantification may have a role in diverse settings we have assessed the assay in a cohort of patients derived from both the England bowel cancer screening programme (BCSP) and symptomatic individuals presenting to secondary care. Method. Patients undergoing colonoscopy provided faecal samples prior to bowel preparation. Faecal tM2-PK concentrations were measured by ELISA. Sensitivity, specificity, positive predictive value, negative predictive value and ROC analyses were calculated. Results. Ninety-six patients returned faecal samples: 50 of these with adenomas and 7 with cancer. Median age was 68. Median faecal tM2-PK concentration was 3.8 U/mL for individuals without neoplastic findings at colonoscopy, 7.7 U/mL in those with adenomas and 24.4 U/mL in subjects with colorectal cancer (both, p=0.01). ROC analysis demonstrated an AUROC of 0.66 (sensitivity 72.4%, specificity 48.7%, positive predictive value 67.7%, negative predictive value 36.7%). Amongst BCSP patients with a prior positive FOBt faecal tM2-PK was more abundant (median 6.4 U/mL, p=0.03) and its diagnostic accuracy was greater (AUROC 0.82). Conclusion. Our findings confirm that faecal tM2-PK ELISA may have utility as an adjunct to FOBt in a screening context, but do not support its use in symptomatic patients. Abbreviations: BCSP: Bowel cancer screening programme; EMR: Endoscopic mucosal resection; FAP: Familial adenomatous polyposis; FOBt: Faecal occult blood testing; NHS: National Health Service; tM2-PK: tumour M2-pyruvate kinase.

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The discovery and validation of colorectal cancer biomarkers

Phung

Nice

2010

Biomedical Chromatography

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Colorectal cancer is currently the third most common malignancy in the world. Patients have excellent prognosis following surgical resection if their tumour is still localized at diagnosis. By contrast, once the tumour has started to metastasize, prognosis is much poorer. Accurate early detection can therefore significantly reduce the mortality from this disease. However, current tests either lack the required sensitivity and selectivity or are costly and invasive. Improved biomarkers, or panels of biomarkers, are therefore urgently required. We have addressed current screening strategies and potential protein biomarkers that have been proposed. The role of both discovery and hypothesis-driven proteomics approaches for biomarker discovery and validation is discussed. Using such approaches we show how multiple reaction monitoring (MRM) can be successfully developed and used for quantitative multiplexed analysis of potential faecal biomarkers.

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Colorectal cancer screening by non-invasive metabolic biomarker fecal tumor M2-PK

Abstract: Fecal tumor M2-PK is an appropriately sensitive tool to pre-select those patients requiring colonoscopy for the further diagnostic confirmation or exclusion of colorectal cancer.

Cited by 57 publications

References 27 publications

Sensitivity and specificity of faecal tumour M2 pyruvate kinase for detection of colorectal adenomas in a large screening study

Sensitivity and specificity of faecal tumour M2 pyruvate kinase for detection of colorectal adenomas in a large screening study

Correlation between Faecal Tumour M2 Pyruvate Kinase and Colonoscopy for the Detection of Adenomatous Neoplasia in a Secondary Care Cohort

The discovery and validation of colorectal cancer biomarkers

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