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Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma.

Hu W, Lu SX, Li M, Zhang C, Liu LL, Fu J, Jin JT, Luo RZ, Zhang CZ, Yun JP - Oncotarget (2015)

Bottom Line: PKM2 depletion decreased the degradation of Bim.Combination of PKM2 and Bim levels had the best prognostic significance.We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT
Pyruvate kinase M2 (PKM2) contributes to the Warburg effect, a hallmark of cancer. We showed that PKM2 levels were correlated with overall survival (hazard ration = 1.675, 95% confidence interval: 1.389-2.019, P < 0.001) and disease-free survival (hazard ration = 1.573, 95% confidence interval: 1.214-2.038, P < 0.001) in a cohort of 490 patients with HCC. The correlations were further validated in an independent cohort of 148 HCC patients. Multivariate analyses revealed that PKM2 was an independent indicator of poor outcome in HCC. The knockdown of PKM2 in HCC cells inhibited cell proliferation and induced apoptosis in vitro and in vivo. Bim siRNA markedly abolished the PKM2-depletion-induced apoptosis. PKM2 depletion decreased the degradation of Bim. In clinical samples, PKM2 expression was reversely correlated with Bim expression. Combination of PKM2 and Bim levels had the best prognostic significance. We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

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Related in: MedlinePlus

PKM2 expression is reversely correlated with Bim expression in clinical samples(A) The relationship of PKM2 and Bim in 490 patients with HCC was determined by IHC. Representative immunohistochemical images of PKM2 and Bim were shown. (B) Spearman correlation analysis showed the relationship of PKM2 and Bim expression. The p value was generated using χ2 test. (C) The prognostic value of Bim was determined by Kaplan–Meier analysis. (D) HCC cases were divided into 3 groups according to the combination of PKM2 and Bim expression. Kaplan–Meier analysis was conducted to estimate of overall survival of the patients in the 3 groups.
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Figure 6: PKM2 expression is reversely correlated with Bim expression in clinical samples(A) The relationship of PKM2 and Bim in 490 patients with HCC was determined by IHC. Representative immunohistochemical images of PKM2 and Bim were shown. (B) Spearman correlation analysis showed the relationship of PKM2 and Bim expression. The p value was generated using χ2 test. (C) The prognostic value of Bim was determined by Kaplan–Meier analysis. (D) HCC cases were divided into 3 groups according to the combination of PKM2 and Bim expression. Kaplan–Meier analysis was conducted to estimate of overall survival of the patients in the 3 groups.

Mentions: To explore the relationship between PKM2 and Bim expression in clinical samples, the expression of PKM2 and Bim was analyzed in a large cohort of 490 patients with HCC. Results showed cases with high PKM2 expression in tumor tissues were frequently with low Bim expression (Figure 6A). Statistically, PKM2 expression was significantly reversely associated with Bim expression (Figure 6B, P < 0.0001).


Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma.

Hu W, Lu SX, Li M, Zhang C, Liu LL, Fu J, Jin JT, Luo RZ, Zhang CZ, Yun JP - Oncotarget (2015)

PKM2 expression is reversely correlated with Bim expression in clinical samples(A) The relationship of PKM2 and Bim in 490 patients with HCC was determined by IHC. Representative immunohistochemical images of PKM2 and Bim were shown. (B) Spearman correlation analysis showed the relationship of PKM2 and Bim expression. The p value was generated using χ2 test. (C) The prognostic value of Bim was determined by Kaplan–Meier analysis. (D) HCC cases were divided into 3 groups according to the combination of PKM2 and Bim expression. Kaplan–Meier analysis was conducted to estimate of overall survival of the patients in the 3 groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4466635&req=5

Figure 6: PKM2 expression is reversely correlated with Bim expression in clinical samples(A) The relationship of PKM2 and Bim in 490 patients with HCC was determined by IHC. Representative immunohistochemical images of PKM2 and Bim were shown. (B) Spearman correlation analysis showed the relationship of PKM2 and Bim expression. The p value was generated using χ2 test. (C) The prognostic value of Bim was determined by Kaplan–Meier analysis. (D) HCC cases were divided into 3 groups according to the combination of PKM2 and Bim expression. Kaplan–Meier analysis was conducted to estimate of overall survival of the patients in the 3 groups.
Mentions: To explore the relationship between PKM2 and Bim expression in clinical samples, the expression of PKM2 and Bim was analyzed in a large cohort of 490 patients with HCC. Results showed cases with high PKM2 expression in tumor tissues were frequently with low Bim expression (Figure 6A). Statistically, PKM2 expression was significantly reversely associated with Bim expression (Figure 6B, P < 0.0001).

Bottom Line: PKM2 depletion decreased the degradation of Bim.Combination of PKM2 and Bim levels had the best prognostic significance.We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

View Article: PubMed Central - PubMed

Affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.

ABSTRACT
Pyruvate kinase M2 (PKM2) contributes to the Warburg effect, a hallmark of cancer. We showed that PKM2 levels were correlated with overall survival (hazard ration = 1.675, 95% confidence interval: 1.389-2.019, P < 0.001) and disease-free survival (hazard ration = 1.573, 95% confidence interval: 1.214-2.038, P < 0.001) in a cohort of 490 patients with HCC. The correlations were further validated in an independent cohort of 148 HCC patients. Multivariate analyses revealed that PKM2 was an independent indicator of poor outcome in HCC. The knockdown of PKM2 in HCC cells inhibited cell proliferation and induced apoptosis in vitro and in vivo. Bim siRNA markedly abolished the PKM2-depletion-induced apoptosis. PKM2 depletion decreased the degradation of Bim. In clinical samples, PKM2 expression was reversely correlated with Bim expression. Combination of PKM2 and Bim levels had the best prognostic significance. We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

Show MeSH
Related in: MedlinePlus