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.

女性结直肠癌 (CRC) 的发病率低于男性，但右侧结肠癌 (RCC) 的发病率较高。这是令人担忧的，因为在所有 CRC 患者中，RCC 患者的临床结果最差。异常代谢是癌症的已知标志和治疗靶点。我们提出，由于肿瘤间分子和基因组变异，以及因性别而异的结肠环境环境的差异，CRC 之间存在代谢亚型。患者结肠肿瘤 (n = 197) 和正常组织 (n = 39) 的代谢组学分析揭示了依赖于解剖位置的性别特异性代谢亚型。患有 RCC 的女性的肿瘤营养耗尽，显示出增强的能量产生以促进天冬酰胺合成和氨基酸摄取。ASNS ) 表达与女性较差的存活率相关。这是第一项在 RCC 女性中显示独特的、营养耗尽的代谢亚型的研究，对 CRC 患者的肿瘤进展和结果有影响。