Mrowiec Katarzyna, Debik Julia, Jelonek Karol, Kurczyk Agata, Ponge Lucyna, Wilk Agata, Krzempek Marcela, Giskeødegård Guro F, Bathen Tone F, Widłak Piotr
Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, Poland.
Department of Circulation and Medical Imaging, The Norwegian University of Science and Technology, Trondheim, Norway.
Front Oncol. 2024 Apr 4;14:1377373. doi: 10.3389/fonc.2024.1377373. eCollection 2024.
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.
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.
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).
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.
实体癌的进展在系统层面表现为体液代谢组中的分子变化，体液是癌症生物标志物的一个新来源。
我们使用高分辨率质谱法定量分析血清代谢物谱。比较了乳腺癌患者（n = 112）与两组年龄分布相似的健康女性（分别来自波兰和挪威；n = 95和n = 112）的代谢谱。
尽管两组对照之间存在差异，但一组43种代谢物和脂质能够一致地区分乳腺癌患者和健康女性。此外，还分析了患有其他类型实体癌（结直肠癌、头颈癌和肺癌）的较小女性患者群体，发现一组42种代谢物和脂质能够一致地将所有这三种癌症类型与两组健康女性区分开来。这两组的共同部分，可称为多癌特征，包含23种化合物，其中包括几种氨基酸（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（以LPC(18:0)为例）和甘油二酯水平降低。有趣的是，在乳腺癌患者血清中，其他癌症典型的最丰富胆固醇酯（CE(18:2)）浓度降低的情况最不明显。多癌特征中的成分能够建立一个性能良好的乳腺癌分类器，该分类器在独立的女性群体中预测癌症的准确率非常高（AUC>0.95）。
总之，用于区分乳腺癌患者和对照的关键代谢物包括假设的多癌特征成分，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。
