PDF(Pubmed)
Abstract：
UNASSIGNED: The progression of solid cancers is manifested at the systemic level as molecular changes in the metabolome of body fluids, an emerging source of cancer biomarkers.
UNASSIGNED: We analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions.
UNASSIGNED: Despite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95).
UNASSIGNED: In conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.
UNASSIGNED: We analyzed quantitatively the serum metabolite profile using high-resolution mass spectrometry. Metabolic profiles were compared between breast cancer patients (n=112) and two groups of healthy women (from Poland and Norway; n=95 and n=112, respectively) with similar age distributions.
UNASSIGNED: Despite differences between both cohorts of controls, a set of 43 metabolites and lipids uniformly discriminated against breast cancer patients and healthy women. Moreover, smaller groups of female patients with other types of solid cancers (colorectal, head and neck, and lung cancers) were analyzed, which revealed a set of 42 metabolites and lipids that uniformly differentiated all three cancer types from both cohorts of healthy women. A common part of both sets, which could be called a multi-cancer signature, contained 23 compounds, which included reduced levels of a few amino acids (alanine, aspartate, glutamine, histidine, phenylalanine, and leucine/isoleucine), lysophosphatidylcholines (exemplified by LPC(18:0)), and diglycerides. Interestingly, a reduced concentration of the most abundant cholesteryl ester (CE(18:2)) typical for other cancers was the least significant in the serum of breast cancer patients. Components present in a multi-cancer signature enabled the establishment of a well-performing breast cancer classifier, which predicted cancer with a very high precision in independent groups of women (AUC>0.95).
UNASSIGNED: In conclusion, metabolites critical for discriminating breast cancer patients from controls included components of hypothetical multi-cancer signature, which indicated wider potential applicability of a general serum metabolome cancer biomarker.
摘要：
■实体癌的进展在全身水平上表现为体液代谢组的分子变化，癌症生物标志物的新兴来源。
■我们使用高分辨率质谱定量分析了血清代谢物谱。比较了年龄分布相似的乳腺癌患者（n=112）和两组健康女性（分别来自波兰和挪威；n=95和n=112）的代谢谱。
■尽管两个对照组之间存在差异，一组43种代谢物和脂质对乳腺癌患者和健康女性均有区别。此外，较小的女性患者组患有其他类型的实体癌(结直肠癌，头部和颈部,和肺癌)进行了分析，该研究揭示了一组42种代谢物和脂质，它们从两个健康女性队列中均匀区分了所有三种癌症类型。这两组的共同部分，这可以称为多癌签名，包含23种化合物，其中包括少量氨基酸(丙氨酸，天冬氨酸,谷氨酰胺,组氨酸,苯丙氨酸,和亮氨酸/异亮氨酸），溶血磷脂酰胆碱（例如LPC（18：0）），和甘油二酯。有趣的是,在乳腺癌患者的血清中，其他癌症典型的最丰富的胆固醇酯（CE（18：2））的浓度降低是最不重要的。多种癌症特征中存在的成分使得能够建立一个性能良好的乳腺癌分类器，在独立的女性群体中以非常高的精度预测癌症(AUC>0.95)。
■总而言之，对区分乳腺癌患者与对照组至关重要的代谢物包括假设的多癌特征的成分，这表明一般血清代谢组癌症生物标志物具有更广泛的潜在适用性。
■我们使用高分辨率质谱定量分析了血清代谢物谱。比较了年龄分布相似的乳腺癌患者（n=112）和两组健康女性（分别来自波兰和挪威；n=95和n=112）的代谢谱。
■尽管两个对照组之间存在差异，一组43种代谢物和脂质对乳腺癌患者和健康女性均有区别。此外，较小的女性患者组患有其他类型的实体癌(结直肠癌，头部和颈部,和肺癌)进行了分析，该研究揭示了一组42种代谢物和脂质，它们从两个健康女性队列中均匀区分了所有三种癌症类型。这两组的共同部分，这可以称为多癌签名，包含23种化合物，其中包括少量氨基酸(丙氨酸，天冬氨酸,谷氨酰胺,组氨酸,苯丙氨酸,和亮氨酸/异亮氨酸），溶血磷脂酰胆碱（例如LPC（18：0）），和甘油二酯。有趣的是,在乳腺癌患者的血清中，其他癌症典型的最丰富的胆固醇酯（CE（18：2））的浓度降低是最不重要的。多种癌症特征中存在的成分使得能够建立一个性能良好的乳腺癌分类器，在独立的女性群体中以非常高的精度预测癌症(AUC>0.95)。
■总而言之，对区分乳腺癌患者与对照组至关重要的代谢物包括假设的多癌特征的成分，这表明一般血清代谢组癌症生物标志物具有更广泛的潜在适用性。
