dataset
posted on 2023-03-31, 02:23 authored by Yasmin Kamal, Stephanie L. Schmit, Hannah J. Hoehn, Christopher I. Amos, H. Robert Frost Table S7. Pathway enrichment differences between CRC primary tumors and metastases (lung and liver) in the MCC and Consortium datasets after adjusting for age, sex, treatment exposure status, and anatomical origin in the tissue sensitive setting: Hallmark and C2 Collections. Table S8. Top 500 differentially expressed genes between CRC primary tumors and metastases (liver and lung) in the tissue sensitive setting for the MCC and Consortium datasets while adjusting for age, sex, anatomical origin, and treatment exposure status in the tissue sensitive setting. We also computed a Fischer's meta-analysis for the top 500 genes enriched in both the MCC and Consortium datasets. Table S9. Pathway enrichment differences between CRC primary tumors and metastases (liver and lung) while adjusting for microsatellite instability (MSI) status in the MCC dataset in the tissue sensitive setting: Hallmark and C2 Collections.
Funding
Norris Cotton Cancer Center
NIH
NCI
History
ARTICLE ABSTRACT
Approximately 20% of colorectal cancer patients with colorectal adenocarcinomas present with metastases at the time of diagnosis, and therapies that specially target these metastases are lacking. We present a novel approach for investigating transcriptomic differences between primary colorectal adenocarcinoma and distant metastases, which may help to identify primary tumors with high risk for future dissemination and to inform the development of metastasis-targeted therapies. To effectively compare the transcriptomes of primary colorectal adenocarcinoma and metastatic lesions at both the gene and pathway levels, we eliminated tissue specificity of the "host" organs where tumors are located and adjusted for confounders such as exposure to chemotherapy and radiation, and identified that metastases were characterized by reduced epithelial–mesenchymal transition (EMT) but increased MYC target and DNA-repair pathway activities. FBN2 and MMP3 were the most differentially expressed genes between primary tumors and metastases. The two subtypes of colorectal adenocarcinoma metastases that were identified, EMT inflammatory and proliferative, were distinct from the consensus molecular subtype (CMS) 3, suggesting subtype exclusivity. In summary, this study highlights transcriptomic differences between primary tumors and colorectal adenocarcinoma metastases and delineates pathways that are activated in metastases that could be targeted in colorectal adenocarcinoma patients with metastatic disease.
These findings identify a colorectal adenocarcinoma metastasis-specific gene-expression signature that is free from potentially confounding background signals coming from treatment exposure and the normal host tissue that the metastasis is now situated within.