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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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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