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Mol Cancer Res. 2019 Feb;17(2):476-487. doi: 10.1158/1541-7786.MCR-18-0601. Epub 2018 Nov 6.

Molecular Correlates of Metastasis by Systematic Pan-Cancer Analysis Across The Cancer Genome Atlas.

Author information

1
Division of Biostatistics, Dan L. Duncan Comprehensive Cancer Center Baylor College of Medicine, Houston, Texas.
2
Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
3
Department of Pathology, Molecular and Cellular Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
4
Division of Biostatistics, Dan L. Duncan Comprehensive Cancer Center Baylor College of Medicine, Houston, Texas. creighto@bcm.edu.
5
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.
7
Department of Medicine, Baylor College of Medicine, Houston, Texas.

Abstract

Tumor metastasis is a major contributor to mortality of cancer patients, but the process remains poorly understood. Molecular comparisons between primary tumors and metastases can provide insights into the pathways and processes involved. Here, we systematically analyzed and cataloged molecular correlates of metastasis using The Cancer Genome Atlas (TCGA) datasets across 11 different cancer types, these data involving 4,473 primary tumor samples and 395 tumor metastasis samples (including 369 from melanoma). For each cancer type, widespread differences in gene transcription between primary and metastasis samples were observed. For several cancer types, metastasis-associated genes from TCGA comparisons were found to overlap extensively with external results from independent profiling datasets of metastatic tumors. Although some differential expression patterns associated with metastasis were found to be shared across multiple cancer types, by and large each cancer type showed a metastasis signature that was distinctive from those of the other cancer types. Functional categories of genes enriched in multiple cancer type-specific metastatic overexpression signatures included cellular response to stress, DNA repair, oxidation-reduction process, protein deubiquitination, and receptor activity. The TCGA-derived prostate cancer metastasis signature in particular could define a subset of aggressive primary prostate cancer. Transglutaminase 2 protein and mRNA were both elevated in metastases from breast and melanoma cancers. Alterations in miRNAs and in DNA methylation were also identified. IMPLICATIONS: Our findings suggest that there are different molecular pathways to metastasis involved in different cancers. Our catalog of alterations provides a resource for future studies investigating the role of specific genes in metastasis.

PMID:
30401717
PMCID:
PMC6359982
[Available on 2020-02-01]
DOI:
10.1158/1541-7786.MCR-18-0601

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