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Published on: July 1, 2013
Acute-phase plasma proteomics of rabbit lung VX2 tumors treated by image-guided microwave ablation
Lin Cheng1,2, Jin-Zhao Peng1, Sheng-Wei Li1
1Department of Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Purpose:
To explore the plasma proteomic changes of rabbit lung VX2 tumors treated by microwave ablation, and to explore the molecular pathway mechanisms that may be involved.
Methods:
New Zealand white rabbits were inoculated with VX2 tumor cell suspension in the right lower lung and treated with microwave ablation after 2-3 weeks of tumor formation. Blood was collected at 5 time points (TP1~TP5) before and after ablation by cardiac blood sampling and pre-treated before proteomic analysis. The plasma proteome was analyzed by Data-Independent Acquisition (DIA).
Results:
Different molecular pathways were activated at different time points:(i) TP1vsTP2: more proteins were down-regulated and enrichment analysis showed that the proteasome pathway was activated. The abnormal protein folding process involved in this pathway is closely related to the process of tumor development. (ii) TP2vsTP3: more proteins were up-regulated although the number of differentially differentiated proteins was lower and enrichment analysis showed that the phagosome pathway was activated. After microwave ablation inactivates tumor cells, it activates the phagosomal pathway for immune clearance of necrotic tumor tissue. (iii) TP3vsTP4: more down-regulated proteins, enrichment analysis showed that cysteine and methionine metabolism pathway was activated. Decreased metabolism of these amino acids suggests that cancer progression may be blocked after microwave ablation therapy. (iv) TP4vsTP5: the number of differential proteins was less and more down-regulated proteins, enrichment analysis showed that glutathione metabolism and metabolism of xenobiotics by cytochrome P450 pathway were activated. The down-regulated proteins in this pathway may suggest that microwave ablation may have reduced resistance to certain chemotherapeutic agents following.
Conclusions:
In the process of lung cancer treatment by microwave ablation, the changes of proteins on the possible molecular pathways at each time point are related to lung cancer, and not only involve some simple inflammatory reactions, and some of the proteins released by destroying the tumor cells can be used as possible drug binding sites and reduce drug resistance.
Insights
Microwave ablation for lung cancer alters plasma proteins, activating pathways like proteasome and phagosome. These changes may block cancer progression and reduce drug resistance.
Area of Science:
- Oncology
- Proteomics
- Molecular Biology
Background:
- Lung cancer remains a leading cause of cancer-related mortality worldwide.
- Microwave ablation (MWA) is an emerging minimally invasive treatment for localized tumors.
- Understanding the systemic molecular response to MWA is crucial for optimizing treatment strategies.
Purpose of the Study:
- To investigate plasma proteomic alterations in rabbits with lung VX2 tumors following MWA.
- To elucidate the molecular pathway mechanisms associated with these proteomic changes.
Main Methods:
- VX2 lung tumors were established in New Zealand white rabbits.
- Tumors were treated with MWA, and plasma samples were collected at five time points.
- Plasma proteomic analysis was performed using Data-Independent Acquisition (DIA).
Main Results:
- Proteasome pathway activation observed early post-ablation, linked to abnormal protein folding.
- Phagosome pathway activation indicated immune clearance of necrotic tumor tissue.
- Cysteine/methionine metabolism and glutathione/xenobiotic metabolism pathways were modulated, suggesting blocked progression and potential impact on drug resistance.
Conclusions:
- MWA induces complex plasma proteomic changes in lung cancer, extending beyond simple inflammation.
- Specific protein alterations may serve as biomarkers for treatment response.
- MWA-induced changes could potentially enhance sensitivity to certain chemotherapeutic agents.
