Tumor M2 Pyruvate Kinase in Plasma of Patients with Urological Tumors

Roigas, Jan; Schulze, G; Raytarowski, S.; Jung, Klaus; Schnorr, Dietmar; Loening, Stefan A.

doi:10.1159/000050628

Cited by 29 publications

(24 citation statements)

References 3 publications

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“…Additionally, we also found no correlation to PSA levels, TNM system and Gleason Score. Similar results were obtained in a separate study [15]. In TCC we found no higher levels of TuM2-PK in comparison to the control group.…”

Section: Discussionsupporting

confidence: 91%

Pyruvate Kinase Type Tumor M2 in Urological Malignancies

Hegele¹,

Varga²,

Kosche

et al. 2003

Urol Int

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Introduction: The dimeric form of pyruvate kinase type M2 is overexpressed in tumor cells (TuM2-PK). The aim of the present study was to evaluate the clinical value of TuM2-PK as a tumor marker for renal cell carcinoma (RCC), transitional cell carcinoma of the bladder (TCC) and prostate cancer (PCA) by using a commercially available enzyme-linked immunosorbent assay for detection of TuM2-PK in plasma. Material and Methods: The TuM2-PK concentration in EDTA plasma was determined quantitatively and immunologically using an ELISA (ScheBo^®Tech, Germany). We measured the TuM2-PK plasma levels of 83 patients with RCC, 30 patients with TCC and 30 patients with PCA before any therapy. 100 patients with various non-malignant urological disorders were recruited as the control group. Results: Only patients with RCC showed significantly elevated plasma levels of TuM2-PK compared to the control group (p < 0.01). We found a sensitivity of 42.6% and a specificity of 80.4% using a cut-off value of 15 U/ml (manufacturer’s recommendation). During follow-up, only 50% showed increasing plasma levels of TuM2-PK in case of metastases. Significant differences could not be detected in either TCC or PCA. Conclusions: Our data suggest that TuM2-PK is not a useful marker for TCC and PCA. Due to low sensitivity and specificity, TuM2-PK is not suitable for the diagnosis of RCC. Whether TuM2-PK may be useful in advanced RCC to control success of palliative treatment regimens is still unclear.

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Section: Discussionsupporting

confidence: 91%

Pyruvate Kinase Type Tumor M2 in Urological Malignancies

Hegele¹,

Varga²,

Kosche

et al. 2003

Urol Int

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“…Christofk et al observed that stable knockdown of pyruvate kinase M2 isoform (PKM2) in the human lung cancer cell line H1299 resulted in decreased rates of glucose metabolism and reduced cell proliferation (17). These results were echoed in clinical studies reported by Roigas et al, who observed that PKM2 levels in patients with malignant renal tumors were significantly higher than in healthy donors (114). In addition, PKM2 has been shown to be capable of predicting disease recurrence in renal cell carcinoma patients after nephrectomy (95).…”

Section: Sod and Cell Metabolism In Cancer Preventionmentioning

confidence: 82%

Manganese Superoxide Dismutase in Cancer Prevention

Robbins

Zhao

2014

Antioxidants & Redox Signaling

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Significance: Cancer is the second leading cause of death in the United States. Considering the quality of life and treatment cost, the best way to fight against cancer is to prevent or suppress cancer development. Cancer is preventable as indicated by human papilloma virus (HPV) vaccination and tamoxifen/raloxifen treatment in breast cancer prevention. The activities of superoxide dismutases (SODs) are often lowered during early cancer development, making it a rational candidate for cancer prevention. Recent Advances: SOD liposome and mimetics have been shown to be effective in cancer prevention animal models. They've also passed safety tests during early phase clinical trials. Dietary supplement-based SOD cancer prevention provides another opportunity for antioxidant-based cancer prevention. New mechanistic studies have revealed that SOD inhibits not only oncogenic activity, but also subsequent metabolic shifts during early tumorigenesis. Critical Issues: Lack of sufficient animal model studies targeting specific cancers; and lack of clinical trials and support from pharmaceutical industries also hamper efforts in further advancing SOD-based cancer prevention. Future Directions: To educate and obtain support from our society that cancer is preventable. To combine SOD-based therapeutics with other cancer preventive agents to obtain synergistic effects. To formulate a dietary supplementation-based antioxidant approach for cancer prevention. Lastly, targeting specific populations who are prone to carcinogens, which can trigger oxidative stress as the mechanism of carcinogenesis. Antioxid. Redox Signal. 20, 1628-1645.

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“…In lung cancer, a metaanalysis revealed that M2-PK can be a potential biomarker for diagnosis of non-small cell lung cancer with pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) of 0.69 (0.65-0.72), 0.92 (0.89-0.94), 7.84 (5.92-10.38), and 0.36 (0.32-0.40) [37]. In addition to the previous non-metastatic cancers, plasma M2-PK concentrations might be a potential biomarker of advanced renal cell cancer with a sensitivity of 66.7% and specificity of 95% [40].…”

Section: Discussionmentioning

confidence: 99%

“…The mean sensitivity and specificity (0.76 and 0.80) of M2-PK were even higher than those of ERCP (0.74 and 0.70) [54], the current benchmark of BTC pretreatment diagnosis [4]. Though the LR showed imperfect robustness as a lonely marker [39][40][41][51][52][53], this easy available M2-PK test is highly recommended alongside conventional cytological and histological examinations for BTC by Navaneethan et al They found that a combination of markers -elevated M2-PK (>109.1 U/l) or CA 19-9 (>33 U/ml) or positive biliary brushing increased the sensitivity (88.2%) and the specificity (88.2%) in diagnosing malignant biliary strictures, with an AUC of 0.89 [25]. In another study, combined M2-PK with CA19-9 did not improve the diagnostic sensitivity and specificity over the M2-PK alone [26].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, M2-PK specifically assists survival and development of cellular growth of tumor cells [29]. Its role as a diagnostic marker has been explored in many different cancers and diseases such as Barret's esophageal cancer [30,31], glioma [32], gastric cancer [29,33], colon cancer [34,35], non-small cell lung cancer [36,37], exocrine pancreatic cancer [38], ovarian cancer [39] and advanced renal cancer [40], with diagnostic sensitivity levels ranging from 43 to 95%.…”

Section: Introductionmentioning

confidence: 99%

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The Diagnostic Value of Pyruvate Kinase Isoenzyme Type M2 for Biliary Tract Carcinoma. A Systematic Review and Meta-Analysis

Wang

Liu

Zhang

et al. 2018

JGLD

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Background & Aims: Growing evidence has shown that M2-PK is involved in cancer diagnosis and prognosis. The overall diagnostic accuracy of the pyruvate kinase isoenzyme type M2 (M2-PK) in biliary tract carcinoma (BTC) remains controversial. We performed a meta-analysis to evaluate the diagnostic value of M2-PK for BTC.Methods: The online PubMed, Cochrane, Web of Science, and Embase databases were searched for eligible studies published until August 8th, 2017. The Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate study quality. All statistical analyses were conducted with Stata 12.0.Results: We included 7 studies from 5 articles with 410 patients with BTC and 438 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for M2-PK in the diagnosis of BTC were 0.79 (95%CI 0.70-0.86), 0.81 (95%CI 0.71-0.88), 4.1 (95%CI 2.5-6.8), 0.26 (95%CI 0.16-0.41), 17.159 (95%CI 5.468-54.071), and 0.87 (95%CI 0.83-0.89), respectively. The same indicators assessed for CA19-9 were as follows: 0.70 (95%CI 0.62-0.77), 0.71 (95%CI 0.45-0.87), 2.38 (95%CI 1.2-4.73), 0.43 (95%CI 0.34-0.53), 6.28 (95%CI 2.4-16.44) and 0.73 (95%CI 0.69-0.77), respectively. Additionally, the diagnostic value of M2-PK varied based on characteristics of golden methods and different cut-off values.Conclusions: This meta-analysis showed that M2-PK had a better diagnostic accuracy for BTC compared with CA19-9, with moderate diagnostic performance. However, prospective studies are required to confirm its diagnostic value.

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Tumor M2 Pyruvate Kinase in Plasma of Patients with Urological Tumors

Cited by 29 publications

References 3 publications

Pyruvate Kinase Type Tumor M2 in Urological Malignancies

Pyruvate Kinase Type Tumor M2 in Urological Malignancies

Manganese Superoxide Dismutase in Cancer Prevention

The Diagnostic Value of Pyruvate Kinase Isoenzyme Type M2 for Biliary Tract Carcinoma. A Systematic Review and Meta-Analysis

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