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Pyruvate Kinase Muscle Isoenzyme 2 (PKM2) Expression Is Associated with Overall Survival in Pancreatic Ductal Adenocarcinoma

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Abstract

Purpose

Pyruvate kinase muscle isoenzyme 2 (PKM2) is a key enzyme in aerobic glycolysis and is thought to contribute to cancer cell metabolic reprogramming. The aim of this study was to evaluate PKM2 immunohistochemical expression as a potential prognostic biomarker in pancreatic ductal adenocarcinoma (PDAC).

Methods

A tissue microarray was constructed using surgical specimens for 115 patients who underwent resections for PDAC, stained with PKM2 antibody, and scored for expression level. Statistical analyses were performed to investigate the association between PKM2 and patient survival, tumor stage, tumor grade, surgical margin status, lymph node ratio, perineural invasion status, or the use of adjuvant chemotherapy.

Results

Fifty-three percent of tumors had positive PKM2 expression, and 47 % of tumors had negative PKM2 expression. PKM2 expression was associated with overall survival (HR 0.56, p = 0.007) and CA 19-9 levels (p = 0.035), but was not associated with tumor stage, tumor grade, surgical margin status, lymph node ratio, perineural invasion, or adjuvant chemotherapy use.

Conclusions

PKM2 expression is associated with overall survival in PDAC. Further studies are warranted to validate the value of PKM2 as a prognostic biomarker and to examine the potential utility of PKM2 in predicting treatment response, as well as a potential therapeutic target in PDAC.

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Funding

The project described was supported by Cancer Center Support Grant (CCSG) National Institutes of Health (NIH) P30 CA68485 and Grant UL1 RR024975-01 and is now at the National Center for Advancing Translational Sciences, Grant 2 UL1 TR000445-06. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Conflict of Interest

The authors declare they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Natalie A. Lockney

  2. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Manchao Zhang

  3. Amherst College, Amherst, MA, USA

    Yanzhen Lu

  4. Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA

    Sabrina C. Sopha

  5. Department of Pathology, Vanderbilt University, Nashville, TN, USA

    M. Kay Washington

  6. Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA

    Nipun Merchant

  7. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA

    Zhiguo Zhao & Yu Shyr

  8. Department of Radiation Oncology, Vanderbilt University, Nashville, TN, USA

    A. Bapsi Chakravarthy

  9. Department of Radiation Oncology, The Ohio State University College of Medicine, 300 W 10th Avenue, Columbus, OH, 43210, USA

    Fen Xia

Authors
  1. Natalie A. Lockney
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  2. Manchao Zhang
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  3. Yanzhen Lu
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  4. Sabrina C. Sopha
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  5. M. Kay Washington
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  7. Zhiguo Zhao
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  10. Fen Xia
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Correspondence to Fen Xia.

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Lockney, N.A., Zhang, M., Lu, Y. et al. Pyruvate Kinase Muscle Isoenzyme 2 (PKM2) Expression Is Associated with Overall Survival in Pancreatic Ductal Adenocarcinoma. J Gastrointest Canc 46, 390–398 (2015). https://doi.org/10.1007/s12029-015-9764-6

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  • DOI: https://doi.org/10.1007/s12029-015-9764-6

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