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[High expression of hnRNPAB/Kap1 together promote poor prognosis in HCC]
1Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Insights
Heterogeneous nuclear ribonucleoprotein AB (hnRNP AB) and KRAB-associated protein 1 (Kap1) form complexes in hepatocellular carcinoma (HCC) cells. Their combined expression predicts poor HCC prognosis and recurrence, indicating potential therapeutic targets.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Understanding the molecular mechanisms and protein interactions in HCC is crucial for improving patient outcomes.
- Heterogeneous nuclear ribonucleoprotein AB (hnRNP AB) is implicated in various cellular processes, but its role in HCC requires further elucidation.
Purpose of the Study:
- To identify interaction partners of hnRNP AB in hepatocellular carcinoma (HCC) cells.
- To investigate the clinical significance of hnRNP AB and its interacting proteins in HCC prognosis.
- To explore potential therapeutic targets for HCC based on protein complex formation.
Main Methods:
- Mass spectrometry was employed to identify peptides of KRAB-associated protein 1 (Kap1) interacting with hnRNP AB.
- Immunoprecipitation and western blotting were used to validate the hnRNP AB-Kap1 interaction.
- Immunohistochemical staining on tissue microarrays assessed hnRNPAB/Kap1 protein expression in HCC patients.
Main Results:
- Kap1 was identified as a molecular partner of hnRNP AB in HCC cell lines (HCCLM3 and HepG2).
- High expression of Kap1 correlated with significantly lower 5-year survival rates (36% vs. 59%) and higher recurrence rates (72% vs. 54%) in HCC patients.
- Both hnRNPAB and Kap1, individually or in combination, were identified as independent prognostic indicators for overall survival and time to recurrence in HCC.
Conclusions:
- hnRNP AB and Kap1 form protein complexes within HCC cells.
- The expression levels of hnRNP AB, alone or in conjunction with Kap1, serve as important predictors of HCC prognosis.
- These findings highlight hnRNP AB and Kap1 as potential therapeutic targets for future HCC studies.
Abstract:
Objective: To further understand the interaction protein spectrum of heterogeneous ribonucleoprotein AB (hnRNP AB), and to investigate their clinical significance in hepatocellular carcinoma (HCC). Methods: We carried out mass spectrometry to reveal the specific peptides of KRAB-associated protein 1 (Kap1) and hnRNPAB, and verified their interaction by immunocoprecipitation and western blotting. Expression of hnRNPAB/Kap1 proteins were detected by immunohistochemical staining in the tissue microarrays. Categorical data were analyzed by the chi square test or Fisher exact test; enumeration data between groups were compared using Student t-test or Wilcocon signed rank test; the cumulative recurrence and survival rates were evaluated using the Kaplan-Meier method and the differences were assessed using the log-rank test. Results: We identified Kap1 as a molecular partner for hnRNPAB in HCCLM3 cells and HepG2 cells as well. We found that the 5-year survival rate of the Kap1high patients was significantly lower than the survival rate of those of the Kap1low group (36% vs 59% , HR = 1.67, P < 0.001). Similarly, Kap1high HCC patients had the poorest prognosis at 5-years, with higher cumulative recurrence rate than Kap1low patients (72% vs 54%, HR = 1.66, P = 0.001). Univariate and Multivariate analyses revealed that hnRNPAB /Kap1 alone (HR = 1.35 /1.28, P = 0.001) or in combination with Kap1 (HR =1.24 /1.27, P < 0.05) were independent prognostic indicators for overall survival and time to recurrence. Conclusion: In HCC cells, hnRNPAB and Kap1 form protein complexes. The expression levels of hnRNPAB alone or in combination with Kap1 in HCC patients are important because they provide not only a predictor for HCC prognosis but also a therapeutic target for future studies.
