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.