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

Natalie A. Lockney, Manchao Zhang, Yanzhen Lu, Sabrina C. Sopha, M. Kay Washington, Nipun Merchant, Zhiguo Zhao, Yu Shyr, A. Bapsi Chakravarthy, Fen Xia

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)390-398
Number of pages9
JournalJournal of Gastrointestinal Cancer
Volume46
Issue number4
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

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Pyruvate Kinase
Isoenzymes
Adenocarcinoma
Muscles
Survival
Neoplasms
Adjuvant Chemotherapy
Biomarkers
Lymph Nodes
Glycolysis

Keywords

  • Immunohistochemical expression
  • Pancreatic adenocarcinoma
  • Prognostic biomarker
  • Pyruvate muscle kinase isoenzyme 2

ASJC Scopus subject areas

  • Gastroenterology
  • Oncology

Cite this

Pyruvate Kinase Muscle Isoenzyme 2 (PKM2) Expression Is Associated with Overall Survival in Pancreatic Ductal Adenocarcinoma. / Lockney, Natalie A.; Zhang, Manchao; Lu, Yanzhen; Sopha, Sabrina C.; Washington, M. Kay; Merchant, Nipun; Zhao, Zhiguo; Shyr, Yu; Chakravarthy, A. Bapsi; Xia, Fen.

In: Journal of Gastrointestinal Cancer, Vol. 46, No. 4, 01.12.2015, p. 390-398.

Research output: Contribution to journalArticle

Lockney, NA, Zhang, M, Lu, Y, Sopha, SC, Washington, MK, Merchant, N, Zhao, Z, Shyr, Y, Chakravarthy, AB & Xia, F 2015, 'Pyruvate Kinase Muscle Isoenzyme 2 (PKM2) Expression Is Associated with Overall Survival in Pancreatic Ductal Adenocarcinoma', Journal of Gastrointestinal Cancer, vol. 46, no. 4, pp. 390-398. https://doi.org/10.1007/s12029-015-9764-6
Lockney, Natalie A. ; Zhang, Manchao ; Lu, Yanzhen ; Sopha, Sabrina C. ; Washington, M. Kay ; Merchant, Nipun ; Zhao, Zhiguo ; Shyr, Yu ; Chakravarthy, A. Bapsi ; Xia, Fen. / Pyruvate Kinase Muscle Isoenzyme 2 (PKM2) Expression Is Associated with Overall Survival in Pancreatic Ductal Adenocarcinoma. In: Journal of Gastrointestinal Cancer. 2015 ; Vol. 46, No. 4. pp. 390-398.
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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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AU - Lockney, Natalie A.

AU - Zhang, Manchao

AU - Lu, Yanzhen

AU - Sopha, Sabrina C.

AU - Washington, M. Kay

AU - Merchant, Nipun

AU - Zhao, Zhiguo

AU - Shyr, Yu

AU - Chakravarthy, A. Bapsi

AU - Xia, Fen

PY - 2015/12/1

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N2 - 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.

AB - 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.

KW - Immunohistochemical expression

KW - Pancreatic adenocarcinoma

KW - Prognostic biomarker

KW - Pyruvate muscle kinase isoenzyme 2

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