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Updated: Jun 7, 2025
A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
Intra- and inter-patient diversity in hepatocellular carcinoma based on phosphorylation profiles-A pilot study in a
Kan Toriguchi1, Etsuro Hatano2, Makoto Sudo3
1Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawacho Nishinomiya city, Hyogo, Japan; Department of Surgery, Kobe City Medical Center General Hospital, 2-1-1 Minatojimaminamimachi, Chuo-ku, Kobe, Hyogo, Japan.
Background:
Recent studies have addressed the efficacy of targeted drugs against hepatocellular carcinoma. However, most tumors escape a single kinase inhibition; co-inhibition of additional signaling pathways re-sensitizes resistant cancer cells to targeted drugs, thus reinforcing the importance of combination therapy for drug-resistant tumors. This study aimed to clarify the phosphorylation profiles of representative cancer-related tyrosine kinases in hepatocellular carcinoma to focus on potential therapeutic targets and to investigate the possibility of expanding combination therapy options using targeted drugs.
Materials And Methods:
Patients' whole blood, hepatocellular carcinoma tissue, and adjacent hepatic tissues were obtained during surgeries from 10 patients. All patients showed negative results for hepatitis B and hepatitis C RNA and none had a history of heavy drinking. The activation of receptor tyrosine kinases (RTKs) was analyzed by using a human RTK phosphorylation antibody array.
Results:
Among 62 different phospho-RTKs, 26 were activated in tumor tissues, of which ACK1, Dtk, Fyn, and Lyn were positive in 9 out of 10 cases. The median concordance rates of activated tumor and serum RTKs in each patient was 50 %. There was an inter- and intra-patient diversity of phosphorylation profiles in the serum, tumor of resected specimens, and non-tumor tissue of resected specimens in the same patients.
Conclusion:
There was an intra- and inter- patient diversity in the activation of important and representative cancer-related RTKs. Expanding on this approach will allow us to learn how to predict the best combination of targets for each patient and to prioritize those combinations for clinical testing.
Insights
Hepatocellular carcinoma (HCC) tumors show diverse receptor tyrosine kinase (RTK) activation. Understanding these varied phosphorylation profiles is key to developing effective combination therapies for drug-resistant HCC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Targeted drug efficacy in hepatocellular carcinoma (HCC) is limited by tumor resistance.
- Combination therapy is crucial for overcoming drug resistance in HCC.
- Understanding kinase signaling is vital for developing new HCC treatments.
Purpose of the Study:
- To analyze phosphorylation profiles of cancer-related tyrosine kinases in HCC.
- To identify potential therapeutic targets for HCC.
- To explore expanded combination therapy options for HCC.
Main Methods:
- Analysis of whole blood, HCC tissue, and adjacent hepatic tissues from 10 patients.
- Utilized a human RTK phosphorylation antibody array to assess receptor tyrosine kinase (RTK) activation.
- Patients were screened for hepatitis B/C RNA and heavy drinking history.
Main Results:
- 26 out of 62 phospho-RTKs were activated in tumor tissues.
- ACK1, Dtk, Fyn, and Lyn were activated in 90% of HCC cases.
- Significant inter- and intra-patient diversity in RTK phosphorylation profiles was observed across serum and tissue samples.
Conclusions:
- Significant patient-specific variations exist in cancer-related RTK activation.
- This data supports personalized combination therapy strategies for HCC.
- Further research can predict and prioritize optimal target combinations for clinical trials.
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