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

2020 ◽  
Author(s):  
Farideh Rigi ◽  
Aliakbar Jannatabad ◽  
Azra Izanloo ◽  
Reza Roshanravan ◽  
Hamid Reza Hashemian ◽  
...  

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.

2019 ◽  
Author(s):  
Farideh Rigi ◽  
Aliakbar Jannatabad ◽  
Azra Izanloo ◽  
Reza Roshanravan ◽  
Hamid Reza Hashemian ◽  
...  

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.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Farideh Rigi ◽  
Aliakbar Jannatabad ◽  
Azra Izanloo ◽  
Reza Roshanravan ◽  
Hamid Reza Hashemian ◽  
...  

2018 ◽  
Vol 17 (8) ◽  
pp. 1531-1545 ◽  
Author(s):  
Qingran Li ◽  
Lijuan Cao ◽  
Yang Tian ◽  
Pei Zhang ◽  
Chujie Ding ◽  
...  

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769596 ◽  
Author(s):  
Kejian Zou ◽  
Yaodong Wang ◽  
Yan Hu ◽  
Liansheng Zheng ◽  
Wanfu Xu ◽  
...  

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.


2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 4121-4121
Author(s):  
A. Ginés ◽  
E. Martinez-Balibrea ◽  
C. Plasencia ◽  
A. Martinez-Cardus ◽  
E. Musulén ◽  
...  

2013 ◽  
Vol 12 (1) ◽  
pp. 72 ◽  
Author(s):  
Mohd Iqbal ◽  
Farid Siddiqui ◽  
Vibhor Gupta ◽  
Shilpi Chattopadhyay ◽  
Prakasam Gopinath ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Mariann Rutka ◽  
Renáta Bor ◽  
Anita Bálint ◽  
Anna Fábián ◽  
Ágnes Milassin ◽  
...  

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.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sébastien Coassolo ◽  
Guillaume Davidson ◽  
Luc Negroni ◽  
Giovanni Gambi ◽  
Sylvain Daujat ◽  
...  

AbstractChromodomain helicase DNA binding protein 4 (CHD4) is an ATPase subunit of the Nucleosome Remodelling and Deacetylation (NuRD) complex that regulates gene expression. CHD4 is essential for growth of multiple patient derived melanoma xenografts and for breast cancer. Here we show that CHD4 regulates expression of PADI1 (Protein Arginine Deiminase 1) and PADI3 in multiple cancer cell types modulating citrullination of arginine residues of the allosterically-regulated glycolytic enzyme pyruvate kinase M2 (PKM2). Citrullination of PKM2 R106 reprogrammes cross-talk between PKM2 ligands lowering its sensitivity to the inhibitors Tryptophan, Alanine and Phenylalanine and promoting activation by Serine. Citrullination thus bypasses normal physiological regulation by low Serine levels to promote excessive glycolysis and reduced cell proliferation. We further show that PADI1 and PADI3 expression is up-regulated by hypoxia where PKM2 citrullination contributes to increased glycolysis. We provide insight as to how conversion of arginines to citrulline impacts key interactions within PKM2 that act in concert to reprogramme its activity as an additional mechanism regulating this important enzyme.


2015 ◽  
Vol 34 (4) ◽  
pp. 1933-1942 ◽  
Author(s):  
PARUNYA CHAIYAWAT ◽  
DARANEE CHOKCHAICHAMNANKIT ◽  
KRIENGSAK LIRDPRAPAMONGKOL ◽  
CHANTRAGAN SRISOMSAP ◽  
JISNUSON SVASTI ◽  
...  

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