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Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma

View Article: PubMed Central

ABSTRACT

The identification of prognostic markers for hepatocellular carcinoma (HCC) is needed for clinical practice. Tripartite motif-containing 35 (TRIM35) is a tumor suppressor of HCC. TRIM35 inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells. We found that expression of PKM2 was significantly increased in HCC tissues. This overexpression of PKM2 was correlated with a high TNM stage and level of vascular invasion. Patients with HCC who were positive for PKM2 expression and negative for TRIM35 expression had shorter overall survival and time to recurrence than patients who were negative for PKM2 and positive for TRIM35. Furthermore, PKM2/TRIM35 combination was an independent and significant risk factor for recurrence and survival. In conclusion, PKM2 (+) and TRIM35 (−) contribute to the aggressiveness and poor prognosis of HCC. PKM2/TRIM35 expression could be a biomarker for the prognosis of HCC and target for cancer therapy.

No MeSH data available.


Positive expression of PKM2 and negative expression of TRIM35 significantly correlates with poor prognosis in HCC patients(A, B) Kaplan-Meier analysis of the correlation between PKM2 expression and the recurrence-free or overall survival of 236 patients with HCC. Log-rank tests were used to determine statistical significance. (C, D) Kaplan-Meier analysis of the correlation between TRIM35 expression and the recurrence-free or overall survival. Log-rank tests were used to determine statistical significance.
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Figure 2: Positive expression of PKM2 and negative expression of TRIM35 significantly correlates with poor prognosis in HCC patients(A, B) Kaplan-Meier analysis of the correlation between PKM2 expression and the recurrence-free or overall survival of 236 patients with HCC. Log-rank tests were used to determine statistical significance. (C, D) Kaplan-Meier analysis of the correlation between TRIM35 expression and the recurrence-free or overall survival. Log-rank tests were used to determine statistical significance.

Mentions: In addition, we evaluated the clinical relevance of PKM2 and TRIM35 expression to prognosis in the primary cohort. At the time of last follow-up, 135 and 121 of the 236 patients had tumor recurrence and had died, respectively. Kaplan–Meier analysis showed that the median overall survival (OS) time was 40.3 (95% CI: 33.3–47.4) months for patients with HCC who were positive for PKM2 and 60.8 (95% CI: 56.9–64.6) months for patients with HCC who were negative for PKM2 (P < 0.0001, log rank test, Figure 2A). The median time to recurrence (TTR) was 34.8 (95% CI: 27.5–42.0) months for patients with HCC who were positive for PKM2 and 52.9 (95% CI: 48.4–57.5) months for patients with HCC who were negative for PKM2 (P < 0.0001, log-rank test, Figure 2B). Furthermore, we found that patients with negative TRIM35 expression had shorter OS (47.0 versus 57.7 months, P = 0.017, log-rank test, Figure 2C) and TTR (40.0 versus 50.7 moths, P = 0.025, log-rank test, Figure 2D).


Co-expression of PKM2 and TRIM35 predicts survival and recurrence in hepatocellular carcinoma
Positive expression of PKM2 and negative expression of TRIM35 significantly correlates with poor prognosis in HCC patients(A, B) Kaplan-Meier analysis of the correlation between PKM2 expression and the recurrence-free or overall survival of 236 patients with HCC. Log-rank tests were used to determine statistical significance. (C, D) Kaplan-Meier analysis of the correlation between TRIM35 expression and the recurrence-free or overall survival. Log-rank tests were used to determine statistical significance.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
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getmorefigures.php?uid=PMC4385869&req=5

Figure 2: Positive expression of PKM2 and negative expression of TRIM35 significantly correlates with poor prognosis in HCC patients(A, B) Kaplan-Meier analysis of the correlation between PKM2 expression and the recurrence-free or overall survival of 236 patients with HCC. Log-rank tests were used to determine statistical significance. (C, D) Kaplan-Meier analysis of the correlation between TRIM35 expression and the recurrence-free or overall survival. Log-rank tests were used to determine statistical significance.
Mentions: In addition, we evaluated the clinical relevance of PKM2 and TRIM35 expression to prognosis in the primary cohort. At the time of last follow-up, 135 and 121 of the 236 patients had tumor recurrence and had died, respectively. Kaplan–Meier analysis showed that the median overall survival (OS) time was 40.3 (95% CI: 33.3–47.4) months for patients with HCC who were positive for PKM2 and 60.8 (95% CI: 56.9–64.6) months for patients with HCC who were negative for PKM2 (P < 0.0001, log rank test, Figure 2A). The median time to recurrence (TTR) was 34.8 (95% CI: 27.5–42.0) months for patients with HCC who were positive for PKM2 and 52.9 (95% CI: 48.4–57.5) months for patients with HCC who were negative for PKM2 (P < 0.0001, log-rank test, Figure 2B). Furthermore, we found that patients with negative TRIM35 expression had shorter OS (47.0 versus 57.7 months, P = 0.017, log-rank test, Figure 2C) and TTR (40.0 versus 50.7 moths, P = 0.025, log-rank test, Figure 2D).

View Article: PubMed Central

ABSTRACT

The identification of prognostic markers for hepatocellular carcinoma (HCC) is needed for clinical practice. Tripartite motif-containing 35 (TRIM35) is a tumor suppressor of HCC. TRIM35 inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells. We found that expression of PKM2 was significantly increased in HCC tissues. This overexpression of PKM2 was correlated with a high TNM stage and level of vascular invasion. Patients with HCC who were positive for PKM2 expression and negative for TRIM35 expression had shorter overall survival and time to recurrence than patients who were negative for PKM2 and positive for TRIM35. Furthermore, PKM2/TRIM35 combination was an independent and significant risk factor for recurrence and survival. In conclusion, PKM2 (+) and TRIM35 (&minus;) contribute to the aggressiveness and poor prognosis of HCC. PKM2/TRIM35 expression could be a biomarker for the prognosis of HCC and target for cancer therapy.

No MeSH data available.