Expression of tumor pyruvate kinase M2 isoform in plasma and stool of patients with colorectal cancer or adenomatous polyps

Abstract Background: Tumor pyruvate kinase M2 isoform (tM2-PK), which is an isoform of PK-glycolytic enzyme and appears on the surface of cancerous proliferating cells, has been used as a diagnostic biomarker for colorectal cancer (CRC). The aim of this study was to evaluate the tM2-PK measurement test for the diagnosis of CRCs and adenomatous polyps in plasma and stool samples in an Iranian population. Methods: In this prospective study, a total of 226 stool and 178 plasma samples were received from patients referred to colonoscopy units. tM2-PK enzyme was measured using two separate ScheBo-Biotech-AG ELISA kits for stool and plasma samples. Results: At the cut-off value of 4 U/ml, in tumor group, the sensitivity of fecal tM2-PK test was 100% and the specificity was 68%, and in polyp group, the sensitivity and specificity were 87% and 68%, respectively. At the cut-off value of 15 U/ml in tumor group, the sensitivity of plasma tM2-PK test was 98% and specificity was 74% and in polyp group the sensitivity and specificity were 98% and 74%, respectively. Based on our results, a cut-off range of 4.8-8 U/ml and >8 U/ml could be used to detect polyp and tumor in stool samples, respectively. Similarly, a cut-off range of 19-25 U/ml and >25 U/ml is recommended in plasma samples for polyp and tumor detection, respectively. Conclusions: This study revealed a high specificity and sensitivity of tM2-PK test for stool and plasma samples in patients with CRC and polyps suggesting it as a non-invasive assay to diagnose CRC and adenomatous polyps.

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Expression of tumor pyruvate kinase M2 isoform in plasma and stool of patients with colorectal cancer or adenomatous polyps

10.21203/rs.2.16791/v2 ◽

2020 ◽

Author(s):

Farideh Rigi ◽

Aliakbar Jannatabad ◽

Azra Izanloo ◽

Reza Roshanravan ◽

Hamid Reza Hashemian ◽

...

Keyword(s):

Colorectal Cancer ◽

Pyruvate Kinase ◽

Sensitivity And Specificity ◽

Glycolytic Enzyme ◽

Adenomatous Polyps ◽

Plasma Samples ◽

Polyp Detection ◽

Proliferating Cells ◽

Pyruvate Kinase M2 ◽

Stool Samples

Abstract Background: Tumor pyruvate kinase M2 isoform (tM2-PK), which is an isoform of PK-glycolytic enzyme and appears on the surface of cancerous proliferating cells, has been used as a diagnostic biomarker for colorectal cancer (CRC). The aim of this study was to evaluate the tM2-PK measurement test for the diagnosis of CRCs and adenomatous polyps in plasma and stool samples in an Iranian population. Methods: In this prospective study, a total of 226 stool and 178 plasma samples were received from patients referred to colonoscopy units. tM2-PK enzyme was measured using two separate ScheBo-Biotech-AG ELISA kits for stool and plasma samples. Results: According to ROC curves, in the tumor group, at the cut-off value of 4 U/ml, the sensitivity of fecal tM2-PK test was 100% and the specificity was 68%, and in the polyp group, the sensitivity and specificity were 87% and 68%, respectively. For tumor detection in plasma specimens, a cut-off value >25 U/ml has a sensitivity and specificity of 90.9% and 91.3%, respectively. Similarly, for polyp detection, a cut-off value >19 U/ml has a sensitivity of 96.3% and the specificity of 85.5%. Conclusions: Based on our results, a cut-off range of 4.8-8 U/ml and >8 U/ml could be used to detect polyp and tumor in stool samples, respectively. Similarly, a cut-off range of 19-25 U/ml and >25 U/ml is recommended in plasma samples, suggesting tM2-PK test as a non-invasive assay to diagnose CRC and adenomatous polyps.

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Expression of tumor pyruvate kinase M2 isoform in plasma and stool of patients with colorectal cancer or adenomatous polyps

BMC Gastroenterology ◽

10.1186/s12876-020-01377-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Farideh Rigi ◽

Aliakbar Jannatabad ◽

Azra Izanloo ◽

Reza Roshanravan ◽

Hamid Reza Hashemian ◽

...

Keyword(s):

Colorectal Cancer ◽

Pyruvate Kinase ◽

Adenomatous Polyps ◽

Pyruvate Kinase M2

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Butyrate Suppresses the Proliferation of Colorectal Cancer Cells via Targeting Pyruvate Kinase M2 and Metabolic Reprogramming

Molecular & Cellular Proteomics ◽

10.1074/mcp.ra118.000752 ◽

2018 ◽

Vol 17 (8) ◽

pp. 1531-1545 ◽

Cited By ~ 11

Author(s):

Qingran Li ◽

Lijuan Cao ◽

Yang Tian ◽

Pei Zhang ◽

Chujie Ding ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Pyruvate Kinase ◽

Metabolic Reprogramming ◽

Pyruvate Kinase M2 ◽

Colorectal Cancer Cells

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Specific tumor-derived CCL2 mediated by pyruvate kinase M2 in colorectal cancer cells contributes to macrophage recruitment in tumor microenvironment

Tumor Biology ◽

10.1177/1010428317695962 ◽

2017 ◽

Vol 39 (3) ◽

pp. 101042831769596 ◽

Cited By ~ 10

Author(s):

Kejian Zou ◽

Yaodong Wang ◽

Yan Hu ◽

Liansheng Zheng ◽

Wanfu Xu ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Microenvironment ◽

Pyruvate Kinase ◽

Quantitative Polymerase Chain Reaction ◽

Nuclear Factor Κb ◽

Enzyme Linked Immunosorbent Assay ◽

Cancer Tissue ◽

Nuclear Factor ◽

Pyruvate Kinase M2 ◽

Macrophage Recruitment

Development of colorectal cancer has been considered as a result of imbalance of pro- and anti-inflammatory intestinal microenvironment accompanied by macrophage recruitment. Despite macrophages are implicated in remodeling tumor microenvironment, the mechanism of macrophage recruitment is not fully elucidated yet. In this study, we reported clinical association of highly expressed pyruvate kinase M2 in colorectal cancer with macrophage attraction. The conditioned medium from Caco-2 and HT-29 cells with depleted pyruvate kinase M2 dramatically reduced macrophage recruitment, which is reversed by addition of, a critical chemotaxis factor to macrophage migration, rCCL2. Silencing of endogenous pyruvate kinase M2 markedly decreased CCL2 expression and secretion by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Endogenous pyruvate kinase M2 interacted with p65 and mediated nuclear factor-κB signaling pathway and mainly regulated phosphorylation of Ser276 on p65 nuclear factor-κB. In addition, inhibition of macrophage recruitment caused by pyruvate kinase M2 silencing was rescued by ectopic expression of p65. Interestingly, pyruvate kinase M2 highly expressed in colorectal cancer tissue, which is correction with macrophage distribution. Taken together, we revealed a novel mechanism of pyruvate kinase M2 in promoting colorectal cancer progression by recruitment of macrophages through p65 nuclear factor-κB–mediated expression of CCL2.

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Use of a proteomic approach to link pyruvate kinase M2 expression to oxaliplatin resistance in colorectal cancer patients and human cell lines

Journal of Clinical Oncology ◽

10.1200/jco.2008.26.15_suppl.4121 ◽

2008 ◽

Vol 26 (15_suppl) ◽

pp. 4121-4121

Author(s):

A. Ginés ◽

E. Martinez-Balibrea ◽

C. Plasencia ◽

A. Martinez-Cardus ◽

E. Musulén ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Patients ◽

Pyruvate Kinase ◽

Cell Lines ◽

Human Cell ◽

Human Cell Lines ◽

Pyruvate Kinase M2 ◽

Proteomic Approach ◽

Colorectal Cancer Patients

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Diagnostic Accuracy of Five Different Fecal Markers for the Detection of Precancerous and Cancerous Lesions of the Colorectum

Mediators of Inflammation ◽

10.1155/2016/2492081 ◽

2016 ◽

Vol 2016 ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

Mariann Rutka ◽

Renáta Bor ◽

Anita Bálint ◽

Anna Fábián ◽

Ágnes Milassin ◽

...

Keyword(s):

Colorectal Cancer ◽

Diagnostic Accuracy ◽

Sensitivity And Specificity ◽

Fecal Calprotectin ◽

Colorectal Adenomas ◽

Human Hemoglobin ◽

Combined Use ◽

Fecal Markers ◽

Stool Samples ◽

Metalloproteinase 9

Background.Colorectal cancer (CRC) is the second deadliest malignancy worldwide. This study aimed to compare the diagnostic accuracy of different fecal markers in the detection of colorectal adenomas and cancer.Methods.Stool samples of patients referred to colonoscopy were collected for the analysis of tumor M2pyruvate kinase (M2PK), human hemoglobin (Hb), hemoglobin/haptoglobin (Hb/Hp) complex, fecal calprotectin (FC), and matrix metalloproteinase-9 (MMP-9).Results.Sensitivity and specificity of M2PK for adenomas sized > 1 cm were 60% and 67.5% and for CRC were 94.7% and 67.5%. Sensitivity and specificity of iFOBT for adenomas sized ≥ 1 cm were 80% and 72.5% and for CRC were 94.7% and 72.5%. Sensitivity and specificity of Hb/Hp complex for adenomas sized ≥ 1 cm were 80% and 52.9% and for CRC were 100% and 52.9%. Sensitivity of FC and MMP-9 for CRC was 77.8% and 72.2%. Combined use of M2PK, iFOBT, and FC resulted in a sensitivity and specificity of 95% and 47.5% for the detection of adenomas sized ≥ 1 cm.Discussion.In CRC, sensitivity of M2PK, iFOBT, and Hb/Hp complex proved to be high. Combined use of M2PK, iFOBT, and FC may be valuable in the detection of large adenomas.

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A New Biomarker of Fecal Bacteria for Non-Invasive Diagnosis of Colorectal Cancer

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.744049 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yizhou Yao ◽

Haishun Ni ◽

Xuchao Wang ◽

Qixuan Xu ◽

Jiawen Zhang ◽

...

Keyword(s):

Colorectal Cancer ◽

Predictive Model ◽

Clinical Application ◽

Sensitivity And Specificity ◽

Healthy Subjects ◽

Intestinal Flora ◽

Detection Methods ◽

Diagnostic Ability ◽

Non Invasive ◽

Specificity And Sensitivity

BackgroundThe intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer.MethodsSubjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers.ResultsWe screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri (Pc), Gemella morbillorum (Gm), Parvimonas micra (Pm), Cetobacterium somerae (Cs), and Pasteurella stomatis (Ps). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer.ConclusionFecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application.

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