Identification of molecular subtypes of clinically resectable triple-negative breast cancer (TNBC) is of great importance to achieve better clinical outcomes. Inter- and intratumor metabolic heterogeneity improves cancer survival, and the interaction of various metabolic pathways may affect treatment outcome of TNBC. We speculated that TNBC can be categorized into prognostic metabolic subtype according to the expression changes of glycolysis and cholesterol synthesis. The genome, transcriptome, and clinical data were downloaded from the Cancer Genome Atlas and Molecular Taxonomy of Breast Cancer International Consortium and subsequently analyzed by integrated bioinformatics methods. Four subtypes, namely, glycolytic, cholesterogenic, quiescent, and mixed, were classified according to the normalized median expressions of the genes involved in glycolysis and cholesterol synthesis. In the four subtypes, the cholesterogenic type was correlated with the shortest median survival (log rank P = 0.044), while patients with high-expressed glycolytic genes tended to have a longer survival. Tumors with PIK3CA amplification and dynein axonemal heavy chain 2 deletion exhibited higher expressions of cholesterogenic genes than other mutant oncogenes. The expressions of mitochondrial pyruvate carrier MPC1 and MPC2 were the lowest in quiescent tumor, and MPC2 expression was higher in cholesterogenic tumor compared with glycolytic or quiescent tumor (t-test P < 0.001). Glycolytic and cholesterogenic gene expressions were related to the expressions of prognostic genes in some other types of cancers. Classification of glycolytic and cholesterogenic pathways according to metabolic characteristics provides a new understanding to previously identified subtypes of TNBC and could improve personalized treatments based on tumor metabolic profiles.

识别临床可切除的三阴性乳腺癌（TNBC）的分子亚型对于获得更好的临床结果非常重要。肿瘤间和肿瘤内代谢异质性可提高癌症生存率，各种代谢途径的相互作用可能会影响 TNBC 的治疗结果。我们推测TNBC可以根据糖酵解和胆固醇合成的表达变化分为预后代谢亚型。基因组、转录组和临床数据从乳腺癌国际联盟的癌症基因组图谱和分子分类学下载，随后通过综合生物信息学方法进行分析。根据参与糖酵解和胆固醇合成的基因的归一化中值表达，将四种亚型分类，即糖酵解亚型、胆固醇生成亚型、静止亚型和混合亚型。在四种亚型中，胆固醇生成型与最短的中位生存期相关（对数等级P  = 0.044），而糖酵解基因高表达的患者往往有较长的生存期。具有 PIK3CA 扩增和动力蛋白轴丝重链 2 缺失的肿瘤表现出比其他突变癌基因更高的胆固醇生成基因表达。线粒体丙酮酸载体MPC1和MPC2在静止期肿瘤中表达最低，且与糖酵解或静止期肿瘤相比，胆甾醇性肿瘤中MPC2表达较高（t检验P  < 0.001）。糖酵解和胆固醇生成基因表达与一些其他类型癌症中的预后基因表达相关。根据代谢特征对糖酵解和胆固醇生成途径进行分类，为之前确定的 TNBC 亚型提供了新的认识，并可以改善基于肿瘤代谢特征的个性化治疗。