Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Dec;46(4):390-8.
doi: 10.1007/s12029-015-9764-6.

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

Natalie A Lockney  1 , Manchao Zhang  2 , Yanzhen Lu  3 , Sabrina C Sopha  4 , M Kay Washington  5 , Nipun Merchant  6 , Zhiguo Zhao  7 , Yu Shyr  7 , A Bapsi Chakravarthy  8 , Fen Xia  9
Affiliations

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

Natalie A Lockney et al. J Gastrointest Cancer. 2015 Dec.

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.

Keywords: Immunohistochemical expression; Pancreatic adenocarcinoma; Prognostic biomarker; Pyruvate muscle kinase isoenzyme 2.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest The authors declare they have no competing interests.

Figures

Fig. 1
Fig. 1
Representative images of positive and negative controls for PKM2 staining. a Positive IHC staining by PKM2 rabbit antibody (1:800). b Negative IHC staining by rabbit IgG at the same titer as PKM2 antibody
Fig. 2
Fig. 2
Representative images of PKM2 expression intensity. a Negative PKM2 expression, b weak PKM2 expression, c intermediate PKM2 expression, and d strong PKM2 expression at 100× magnification
Fig. 3
Fig. 3
Expression of PKM2 in normal pancreas. Weak to moderate staining of PKM2 is demonstrated in the epithelial cells of the ducts, especially in small and intercalated ducts (long arrows). PKM2 is also expressed in the interspersed islet cells (short arrow)
Fig. 4
Fig. 4
CA19.9 level (a) and lymph node ratio value (b) by PKM2 expression
Fig. 5
Fig. 5
Kaplan-Meier curve for overall survival. PKM2 intensity was associated with overall survival (p=0.006)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Warburg O, Posener K, Negelein E. Ueber den stoffwechsel der tumoren. Biochem Z. 1924;152:319–44.
    1. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009;324:1029–33. - PMC - PubMed
    1. Sutendra G, Michelakis ED. Pyruvate dehydrogenase kinase as a novel therapeutic target in oncology. Front Oncol. 2013;3:38. - PMC - PubMed
    1. Harada K, Saheki S, Wada K, et al. Purification of four pyruvate kinase isoenzymes of rats by affinity elution chromatography. Biochem Biophys Acta. 1978;524:327–39. - PubMed
    1. Noguchi T, Yamada K, Inoue H, et al. The L- and R-type isoenzymes of rate pyruvate kinase are produced from a single gene by use of different promoters. J Biol Chem. 1987;262:14366–71. - PubMed

Publication types

MeSH terms

LinkOut - more resources