Sex differences in colon cancer metabolism reveal a novel subphenotype Journal Article


Authors: Cai, Y.; Rattray, N. J. W.; Zhang, Q.; Mironova, V.; Santos-Neto, A.; Hsu, K. S.; Rattray, Z.; Cross, J. R.; Zhang, Y.; Paty, P. B.; Khan, S. A.; Johnson, C. H.
Article Title: Sex differences in colon cancer metabolism reveal a novel subphenotype
Abstract: Women have a lower incidence of colorectal cancer (CRC) than men, however, they have a higher incidence of right-sided colon cancer (RCC). This is of concern as patients with RCC have the poorest clinical outcomes among all CRC patients. Aberrant metabolism is a known hallmark and therapeutic target for cancer. We propose that metabolic subphenotypes exist between CRCs due to intertumoral molecular and genomic variation, and differences in environmental milieu of the colon which vary between the sexes. Metabolomics analysis of patient colon tumors (n = 197) and normal tissues (n = 39) revealed sex-specific metabolic subphenotypes dependent on anatomic location. Tumors from women with RCC were nutrient-deplete, showing enhanced energy production to fuel asparagine synthesis and amino acid uptake. The clinical importance of our findings were further investigated in an independent data set from The Cancer Genomic Atlas, and demonstrated that high asparagine synthetase (ASNS) expression correlated with poorer survival for women. This is the first study to show a unique, nutrient-deplete metabolic subphenotype in women with RCC, with implications for tumor progression and outcomes in CRC patients. © 2020, The Author(s).
Journal Title: Scientific Reports
Volume: 10
ISSN: 2045-2322
Publisher: Nature Publishing Group  
Date Published: 2020-01-01
Start Page: 4905
Language: English
DOI: 10.1038/s41598-020-61851-0
PUBMED: 32184446
PROVIDER: scopus
PMCID: PMC7078199
DOI/URL:
Notes: Article -- Export Date: 1 April 2020 -- Source: Scopus
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  1. Philip B Paty
    496 Paty
  2. Justin Robert Cross
    111 Cross
  3. Kuo Shun Hsu
    6 Hsu