Medical Oncology Department, Centre Hospitalier Universitaire Sart-Tilman, Liège, Belgium.
Laboratory of Human Genetics, GIGA Research Institute, Liège, Belgium.
J Transl Med. 2019 Jul 23;17(1):239. doi: 10.1186/s12967-019-1984-2.
Indoleamine 2,3-dioxygenase catalyzes the conversion of tryptophan to kynurenine, an immunosuppressive metabolite involved in T regulatory cell differentiation. Indoleamine 2,3-dioxygenase is expressed in many cancer types, including breast cancer. Here, we analyze kynurenine and tryptophan and their ratio in breast cancer patients and healthy controls.
Breast cancer patients and healthy controls were prospectively enrolled in our study. All subjects underwent blood sample withdrawal at diagnosis or on the day of screening mammography for the healthy controls. Plasmatic kynurenine and tryptophan were determined on a TQ5500 tandem mass spectrometer after chromatographic separation.
We enrolled 146 healthy controls and 202 women with stages I-III breast cancer of all subtypes. All patients underwent surgery, 126 underwent neoadjuvant chemotherapy with 43 showing a pathological complete response, and 43 underwent adjuvant chemotherapy. We observed significantly higher plasmatic kynurenine, tryptophan and their ratio for the healthy controls compared to patients with breast cancer. We observed a lower plasmatic tryptophan and a higher kynurenine/tryptophan ratio in hormone receptor-negative patients compared to hormone receptor-positive cancers. Lobular cancers showed a lower ratio than any other histologies. Advanced cancers were associated with a lower tryptophan level and higher grades with an increased kynurenine/tryptophan ratio. Pathological complete response was associated with higher kynurenine values. The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratios were not predictive of survival.
The plasmatic kynurenine, tryptophan and kynurenine/tryptophan ratio could differentiate breast cancer patients from healthy controls. The Kyn/Trp ratio and Trp also showed different values according to hormone receptor status, TNM stage, T grade and histology. These results suggest a rapid metabolism in breast cancer, but no associations with outcome or sensitivity to chemotherapy were observed.
色氨酸 2,3-双加氧酶催化色氨酸转化为犬尿氨酸，犬尿氨酸是一种免疫抑制代谢物，参与调节性 T 细胞分化。色氨酸 2,3-双加氧酶在许多癌症类型中表达，包括乳腺癌。在这里，我们分析了乳腺癌患者和健康对照者的犬尿氨酸、色氨酸及其比值。
前瞻性纳入本研究的乳腺癌患者和健康对照者。所有患者在诊断时或健康对照者行乳腺 X 线筛查当天抽取血样。采用 TQ5500 串联质谱仪在色谱分离后测定血浆犬尿氨酸和色氨酸。
共纳入 146 名健康对照者和 202 名各亚型 I-III 期乳腺癌患者。所有患者均接受手术治疗，126 例接受新辅助化疗，其中 43 例患者达到病理完全缓解，43 例患者接受辅助化疗。与乳腺癌患者相比，健康对照组的血浆犬尿氨酸、色氨酸及其比值明显更高。与激素受体阳性癌症相比，激素受体阴性患者的血浆色氨酸水平较低，犬尿氨酸/色氨酸比值较高。与其他组织学类型相比，小叶癌的比值较低。晚期癌症与较低的色氨酸水平和较高的分级与增加的犬尿氨酸/色氨酸比值相关。病理完全缓解与较高的犬尿氨酸值相关。血浆犬尿氨酸、色氨酸和犬尿氨酸/色氨酸比值不能预测生存。
血浆犬尿氨酸、色氨酸和犬尿氨酸/色氨酸比值可将乳腺癌患者与健康对照者区分开来。根据激素受体状态、TNM 分期、T 分级和组织学，Kyn/Trp 比值和 Trp 也有不同的数值。这些结果表明乳腺癌存在快速代谢，但与预后或对化疗的敏感性无关。
