Natalie A Lockney1, Manchao Zhang2, Yanzhen Lu3, Sabrina C Sopha4, M Kay Washington5, Nipun Merchant6, Zhiguo Zhao7, Yu Shyr7, A Bapsi Chakravarthy8, Fen Xia9. 1. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. 2. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA. 3. Amherst College, Amherst, MA, USA. 4. Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA. 5. Department of Pathology, Vanderbilt University, Nashville, TN, USA. 6. Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. 7. Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA. 8. Department of Radiation Oncology, Vanderbilt University, Nashville, TN, USA. 9. Department of Radiation Oncology, The Ohio State University College of Medicine, 300 W 10th Avenue, Columbus, OH, 43210, USA. fen.xia@osumc.edu.
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.
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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