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Multi-omics characterization and validation of invasiveness-related molecular features across multiple cancer types
- Source :
- Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-17 (2021), Journal of Translational Medicine
- Publication Year :
- 2021
- Publisher :
- BMC, 2021.
-
Abstract
- Background Tumor invasiveness reflects many biological changes associated with tumorigenesis, progression, metastasis, and drug resistance. Therefore, we performed a systematic assessment of invasiveness-related molecular features across multiple human cancers. Materials and methods Multi-omics data, including gene expression, miRNA, DNA methylation, and somatic mutation, in approximately 10,000 patients across 30 cancer types from The Cancer Genome Atlas, Gene Expression Omnibus, PRECOG, and our institution were enrolled in this study. Results Based on a robust gene signature, we established an invasiveness score and found that the score was significantly associated with worse prognosis in almost all cancers. Then, we identified common invasiveness-associated dysregulated molecular features between high- and low-invasiveness score group across multiple cancers, as well as investigated their mutual interfering relationships thus determining whether the dysregulation of invasiveness-related genes was caused by abnormal promoter methylation or miRNA expression. We also analyzed the correlations between the drug sensitivity data from cancer cell lines and the expression level of 685 invasiveness-related genes differentially expressed in at least ten cancer types. An integrated analysis of the correlations among invasiveness-related genetic features and drug response were conducted in esophageal carcinoma patients to outline the complicated regulatory mechanism of tumor invasiveness status in multiple dimensions. Moreover, functional enrichment suggests the invasiveness score might serve as a predictive biomarker for cancer patients receiving immunotherapy. Conclusion Our pan-cancer study provides a comprehensive atlas of tumor invasiveness and may guide more precise therapeutic strategies for tumor patients.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
lcsh:Medicine
Pan-cancer
Biology
medicine.disease_cause
General Biochemistry, Genetics and Molecular Biology
Metastasis
03 medical and health sciences
0302 clinical medicine
Germline mutation
Neoplasms
Internal medicine
microRNA
medicine
Humans
Molecular features
Gene
Multi-omics
Research
Gene Expression Profiling
lcsh:R
Immunity
Cancer
General Medicine
DNA Methylation
Gene signature
Prognosis
medicine.disease
Invasiveness
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
030220 oncology & carcinogenesis
DNA methylation
Carcinogenesis
Subjects
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 19
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Translational Medicine
- Accession number :
- edsair.doi.dedup.....05c80e1ac1301a6247557558940b94b6