Tumor type M2-pyruvate-kinase levels in pleural fluid versus plasma in cancer patients: a further tool to define the need for invasive procedures☆

Elia, Stefano; Massoud, Renato; Guggino, Gianluca; Cristino, Benedetto; Cortese, Claudio; Massimi, Alessia Raffaella De; Zenobi, Rossella

doi:10.1016/j.ejcts.2008.01.014

Cited by 14 publications

(6 citation statements)

References 26 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In particular, PK-M2, a key enzyme in the glycolytic pathway, is overexpressed during multi-step carcinogenesis. This protein is found in blood, pleural effusion, stool, and other body fluids [17][18][19][20][21], and acts as a biomarker for esophagogastric, hepatopancreatobiliary, and colorectal malignancies [17].…”

Section: Discussionmentioning

confidence: 99%

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

et al. 2009

View full text Add to dashboard Cite

5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic agent for colorectal cancer (CRC). However, resistance to this drug is a major obstacle in CRC chemotherapy. Accurate prediction of response to 5-FU would avoid unnecessary chemotherapy and allow the selection of other effective drugs. To identify a candidate predictor of 5-FU resistance, we isolated secreted proteins that were up- or downregulated in a 5-FU-resistant cancer cell line, compared with the parent cell line (SNU-C4), using a stable isotope-coded labeling protocol. For validating the clinical applicability of this method, levels of the identified proteins were determined in the sera of 46 patients treated with 5-FU. In total, 238 proteins with molecular weights ranging from 50 to 75 kDa were identified. Among these, 45 and 35 secreted proteins were up- and downregulated in the 5-FU-resistant cell line, respectively. We observed significant upregulation of glycolytic enzymes, including glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase M2 (PK-M2), transketolase, and NADP(+)-dependent malic enzyme 1. In particular, the level of PK-M2, a key enzyme in the glycolytic pathway, showed an increasing tendency in both sera and tissues from CRC patients displaying no response to 5-FU-based chemotherapy (progressive and stable disease cases), compared with that in complete or partial responders to 5-FU-based chemotherapy; however, it did not reach the statistical significance. In conclusion, increasing pattern of PK-M2 observed with 5-FU resistance induced in vitro and in sera and tissues from CRC patients displaying poor response to 5-FU-based chemotherapy suggest the relevance of dysregulated glycolysis and 5-FU-resistant CRC.

show abstract

Section: Discussionmentioning

confidence: 99%

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In tumors, M2‐PK is found to be mainly in the dimeric form and has therefore been termed “tumor M2‐PK.”5 Currently, the dimeric form can be detected by a specific antibody raised against it which does not react with the tetrameric form. M2‐PK can be detected in different body fluids, such as plasma, stool, and pleural fluid, and may have a role in the diagnosis of solid tumors including lung, ovary, cervix, breast, kidney, gastrointestinal tumors, and melanoma 6‐10. As yet, however, the role of M2‐PK in bile as a marker for BTC has not been investigated.…”

mentioning

confidence: 99%

Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer

Dhar

Damink

Brindley

et al. 2012

Cancer

View full text Add to dashboard Cite

Background and Aim The early diagnosis of biliary tract cancer (BTC) remains challenging and there are few effective therapies. We investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC. Methods Plasma and bile M2-PK concentrations were measured by ELISA in 88 patients with BTC, 79 with benign biliary diseases and 17 healthy controls. M2-PK expression was sought in BTC tissue array by immunohistochemistry. The role of M2-PK in tumour growth, invasion and angiogenesis was evaluated in BTC cell lines by retrovirus-mediated M2-PK transfection and shRNA silencing techniques. Results Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK for malignancy were significantly higher than those for plasma M2-PK and serum CA19-9. M2-PK expression was specific for cancer cells and correlated with microvessel density. M2-PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2-PK in a negatively expressed cell line (HuCCT-1cells) increased cell invasion whereas silencing in a M2-PK positive cell line (TFK cells) decreased tumour nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2-PK transfected cells were added to an in vitro angiogenesis assay whereas supernatants from silenced cells negated tube formation. Conclusions Bile M2-PK is a novel tumour marker for BTC and correlates with tumour aggressiveness and poor outcome. shRNA mediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic target.

show abstract

“…Previous studies have shown that TuM2-PK can be detected in body uids, which may be due to the release of TuM2-PK during tumor necrosis or metastasis [19]. It has been reported that TuM2-PK was signi cantly increased in MPE, which can be used as an index to distinguish BPE and MPE [20]. The results showed that the levels of TuM2-PK in pleural effusion and serum of patients with MPE were signi cantly higher than those of patients with BPE, and increased most signi cantly in SCLC, which was signi cantly higher than those of lung ADC and SCC, while the levels of TuM2-PK in pleural effusion and serum of patients with ADC were also higher than those of patients with SCC, Therefore, TuM2-PK plays a certain role in the typing and diagnosis of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of serum and pleural levels tumor M2-pyruvate kinase in lung cancer patients with pleural effusion

Zhang

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective: To evaluate the diagnostic value of tumor M2-pyruvate kinase (TuM2-PK) and carcinoembryonic antigen (CEA) levels in both pleural effusion and serum in the differential diagnosis of benign and malignant pleural effusion. Methods: This prospective study was conducted among 80 patients with pleural effusion caused by benign disease (BPE group) and 125 patients with malignant pleural effusion associated with lung cancer (MPE group). The levels of TuM2-PK and CEA were measured by using sandwich enzyme-linked immunosorbent assay and electrochemiluminescence. The receiver-operating characteristic curve (ROC) analysis was used to confirm the optimal critical value to evaluate the diagnostic efficiency of TuM2-PK and CEA. Results: The TuM2-PK and CEA levels in pleural effusion and serum, and their ratio (P/S) were higher in MPE group than that in BPE group (P<0.05). In pleural effusion and serum, the diagnostic efficiency of combined TuM2-PK and CEA for MPE was superior to either single detection. Conclusions: The combined detection of TuM2-PK and CEA has a high sensitivity for diagnosis of MPE and provides important information for rapid and accurate diagnosis of patients.

show abstract

Tumor type M2-pyruvate-kinase levels in pleural fluid versus plasma in cancer patients: a further tool to define the need for invasive procedures☆

Cited by 14 publications

References 26 publications

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

Upregulation of glycolytic enzymes in proteins secreted from human colon cancer cells with 5‐fluorouracil resistance

Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer

Evaluation of serum and pleural levels tumor M2-pyruvate kinase in lung cancer patients with pleural effusion

Contact Info

Product

Resources

About