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Overexpression of the M2 isoform of pyruvate kinase is an adverse prognostic factor for signet ring cell gastric cancer

 Jae Yun Lim  ;  Sun Och Yoon  ;  So Young Seol  ;  Soon Won Hong  ;  Jong Won Kim  ;  Seung Ho Choi  ;  Jae Yong Cho 
 WORLD JOURNAL OF GASTROENTEROLOGY, Vol.18(30) : 4037-4043, 2012 
Journal Title
Issue Date
Biomarker ; Gastric cancer ; M2 isoform of pyruvate kinase ; Prognosis ; Signet ring cell carcinoma
Adenocarcinoma/enzymology* ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Carcinoma, Signet Ring Cell/enzymology* ; Carcinoma, Signet Ring Cell/genetics ; Carcinoma, Signet Ring Cell/pathology ; Female ; Gene Expression ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Prognosis ; Pyruvate Kinase/genetics ; Pyruvate Kinase/metabolism* ; RNA, Messenger/metabolism* ; Stomach Neoplasms/enzymology* ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology
AIM: To investigate M2 isoform of pyruvate kinase (PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target. METHODS: All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment. Clinical and pathological information were obtained from the medical records. Gene expression microarray data from 60 cancer and 19 non-cancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA. Tissue microarrays were constructed from 368 gastric cancer patients. Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity. Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated. RESULTS: PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients (log transformed expression level: 7.6 ± 0.65 vs 6.3 ± 0.51, P < 0.001). Moreover, differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers (log transformed expression level: 7.8 ± 0.70 vs 6.7 ± 0.71, P < 0.001). PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368 (39.1%) human gastric cancer cases. PKM2 expression was not related with stage (P = 0.811), but strongly correlated with gastric cancer differentiation (P < 0.001). Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones. Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells; in contrast, signet-ring cell cancers showed only 17.7% PKM2-positive cells. Importantly, PKM2 expression was correlated with shorter overall survival (P < 0.05) independent of stage only in signet-ring cell cancers. CONCLUSION: PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas. Its function and potential as a prognostic marker should be further verified in gastric cancer.
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1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Won(김종원)
Seol, So Young(설소영)
Yoon, Sun Och(윤선옥) ORCID logo https://orcid.org/0000-0002-5115-1402
Lim, Jae Yun(임재윤)
Cho, Jae Yong(조재용) ORCID logo https://orcid.org/0000-0002-0926-1819
Choi, Seung Ho(최승호) ORCID logo https://orcid.org/0000-0002-9872-3594
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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