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Cross-talk between cuproptosis and ferroptosis to identify immune landscape in cervical cancer for mRNA vaccines
Xuchao Zhang1,2, Wenwen Xu1,2, Zi Wang2
1Department of Oncology, The Second Xiangya Hospital, Central South University, No. 72 Xiangya Road, Changsha, 410000, Hunan, China.
Abstract:
Messenger RNA (mRNA)-based vaccines present a promising avenue for cancer immunotherapy; however, their application in cervical cancer remains unexplored. This study investigated the interplay between the regulated cell death pathways of cuproptosis and ferroptosis to advance the development of mRNA vaccines for cervical cancer. We identified key cuproptosis-related and ferroptosis-related genes (CFRGs) from public mRNA profiles and determined their prognostic significance, mutation frequencies, and effect on the immune landscape. Our analysis revealed two distinct subtypes of cervical cancer associated with CFRGs, with differences in prognosis and immune characteristics. Using LASSO, XGBoost, and SVM-RFE methods, we established a 4-gene prognostic signature (TSC22D3, SQLE, ZNF419, and TFRC) to stratify patients based on their risk and determine its correlation with immune microenvironment, mutation profiles, and treatment responses. RT-qPCR validation confirmed the differential expression of these genes in clinical samples. Our findings identify TSC22D3, SQLE, ZNF419, and TFRC as candidate targets for mRNA vaccine development and offer a potential prognostic tool for personalized cervical cancer treatment.
Insights
Messenger RNA (mRNA) vaccines show promise for cervical cancer immunotherapy. This study explored cuproptosis and ferroptosis genes, identifying a 4-gene signature for risk stratification and potential mRNA vaccine targets.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Messenger RNA (mRNA)-based vaccines are a novel approach for cancer immunotherapy.
- Cervical cancer immunotherapy using mRNA vaccines is an underexplored area.
- Regulated cell death pathways, including cuproptosis and ferroptosis, play roles in cancer progression.
Purpose of the Study:
- To investigate the role of cuproptosis-related and ferroptosis-related genes (CFRGs) in cervical cancer.
- To develop a prognostic signature based on CFRGs for cervical cancer patients.
- To identify potential targets for mRNA vaccine development in cervical cancer.
Main Methods:
- Identification and analysis of key CFRGs from public mRNA profiles.
- Prognostic significance, mutation frequency, and immune landscape analysis of CFRGs.
- Development of a 4-gene prognostic signature using LASSO, XGBoost, and SVM-RFE.
- Validation of gene expression using RT-qPCR.
Main Results:
- Two distinct cervical cancer subtypes associated with CFRGs were identified, differing in prognosis and immune characteristics.
- A 4-gene prognostic signature (TSC22D3, SQLE, ZNF419, TFRC) was established to stratify patients by risk.
- The signature correlated with the immune microenvironment, mutation profiles, and treatment responses.
- Differential expression of the signature genes was confirmed in clinical samples.
Conclusions:
- The identified 4-gene signature serves as a potential prognostic tool for personalized cervical cancer treatment.
- TSC22D3, SQLE, ZNF419, and TFRC are candidate genes for developing novel mRNA vaccines against cervical cancer.
- Understanding the interplay of cuproptosis and ferroptosis pathways can advance mRNA vaccine strategies for cervical cancer.
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