Identification of Prognostic Biomarkers for Multiple Solid Tumors Using a Human Villi Development Model
Botao Zhang1,2, Yuanjing Wang3, Hongxia Li4
1Department of Neuro-oncology, Neurosurgery Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Tumors hijack embryonic epithelial-mesenchymal transition (EMT) for metastasis. This study proposes the "off-track theory," suggesting deviations in tumor gene networks from normal development predict malignancy and poor prognosis, identifying novel biomarkers.
Area of Science:
- Developmental Biology
- Cancer Biology
- Genomics
Background:
- Epithelial-mesenchymal transition (EMT) is crucial for embryonic development (trophoblast implantation) and is co-opted by tumors for invasion and metastasis.
- While both processes share EMT characteristics, trophoblast behavior is "physiological metastasis," distinct from malignant tumors.
- Gene co-expression networks underpin both embryonic development and tumorigenesis.
Purpose of the Study:
- To propose and test the "off-track theory," hypothesizing that deviations in tumor gene co-expression networks from those in villi correlate with malignancy and prognosis.
- To investigate gene co-expression networks in villi and solid tumors to identify differences in EMT-related gene usage.
- To identify "off-track genes" and assess their association with patient survival.
Main Methods:
- Comparison of gene co-expression networks between human villi and multiple solid tumors.
- Network functional enrichment analysis to identify shared and distinct EMT-related genes.
- Application of the "off-track theory" to pinpoint differing genes within EMT networks.
- Survival analysis correlating the risk score of "off-track genes" with patient outcomes.
Main Results:
- Both villi and tumors showed significantly enriched EMT pathways, but utilized different sets of genes.
- Identification of "off-track genes" in tumor EMT networks compared to villi.
- A higher risk score associated with "off-track genes" significantly correlated with poorer survival in cancer patients.
Conclusions:
- Villi development serves as a valuable model for understanding cancer development trajectories due to its regulated gene networks.
- Tumorigenesis involves gene co-expression networks that are "off-track" from normal villi development.
- Identified "off-track genes" represent potential prognostic biomarkers and targets for therapeutic intervention in cancer.
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