Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
PeerJ. 2022 Apr 20;10:e13272. doi: 10.7717/peerj.13272. eCollection 2022.
Previous studies have shown the alteration of amino acid (AA) profile in patients with non-small cell lung cancer (NSCLC). However, there is little data regarding AA profile in NSCLC in Chinese population. The aim of this study was to evaluate AA profile in Chinese NSCLC patients, explore its utility in sample classification and further discuss its related metabolic pathways.
The concentrations of 22 AAs in serum samples from 200 patients with NSCLC and 202 healthy controls were determined by liquid chromatography-tandem mass spectrometer (LC-MS/MS). AA levels in different tumor stages and histological types were also discussed. The performance of AA panel in classifying the cases and controls was evaluated in the training data set and validation data set based on the receiver operating characteristic (ROC) curve, and the important metabolic pathways were identified.
The concentrations of tryptophan (Trp), phenylalanine (Phe), isoleucine (Ile), glycine (Gly), serine (Ser), aspartic acid (Asp), asparagine (Asn), cystein (Cys), glutamic acid (Glu), ornithine (Orn) and citrulline (Cit) were significantly altered in NSCLC patients compared with controls (all P-FDR < 0.05). Among these, four AAs including Asp, Cys, Glu and Orn were substantially up-regulated in NSCLC patients (FC ≥ 1.2). AA levels were significantly altered in patients with late-stage NSCLC, but not in those with early-stage when comparing with healthy controls. In terms of histological type, these AAs were altered in both adenocarcinoma and squamous cell carcinoma. For discrimination of NSCLC from controls, the area under the ROC curve (AUC) was 0.80 (95% CI [0.74-0.85]) in the training data set and 0.79 (95%CI [0.71-0.87]) in the validation data set. The AUCs for early-stage and late-stage NSCLC were 0.75 (95% CI [0.68-0.81]) and 0.86 (95% CI [0.82-0.91]), respectively. Moreover, the model showed a better performance in the classification of squamous cell carcinoma (AUC = 0.90, 95% CI [0.85-0.95]) than adenocarcinoma (AUC = 0.77, 95% CI [0.71-0.82]) from controls. Three important metabolic pathways were involved in the alteration of AA profile, including Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism; and Arg biosynthesis.
The levels of several AAs in serum were altered in Chinese NSCLC patients. These altered AAs may be utilized to classify the cases from the controls. Gly, Ser and Thr metabolism; Ala, Asp and Glu metabolism and Arg biosynthesis pathways may play roles in metabolism of the NSCLC patient.
先前的研究表明，非小细胞肺癌（NSCLC）患者的氨基酸（AA）谱发生了改变。然而，关于中国人 NSCLC 患者 AA 谱的数据很少。本研究旨在评估中国 NSCLC 患者的 AA 谱，探讨其在样本分类中的应用，并进一步探讨其相关代谢途径。
采用液相色谱-串联质谱法（LC-MS/MS）测定 200 例 NSCLC 患者和 202 例健康对照者血清样本中 22 种 AA 的浓度。还讨论了不同肿瘤分期和组织学类型的 AA 水平。根据接收者操作特征（ROC）曲线，在训练数据集和验证数据集中评估 AA 谱在病例和对照组分类中的表现，并确定重要的代谢途径。
与对照组相比，NSCLC 患者的色氨酸（Trp）、苯丙氨酸（Phe）、异亮氨酸（Ile）、甘氨酸（Gly）、丝氨酸（Ser）、天冬氨酸（Asp）、天冬酰胺（Asn）、半胱氨酸（Cys）、谷氨酸（Glu）、鸟氨酸（Orn）和瓜氨酸（Cit）浓度明显改变（均 P-FDR<0.05）。其中，Asp、Cys、Glu 和 Orn 等 4 种 AA 明显上调（FC≥1.2）。晚期 NSCLC 患者的 AA 水平明显改变，但与健康对照组相比，早期患者的 AA 水平并未改变。在组织学类型方面，腺癌和鳞癌患者的这些 AA 均发生改变。在区分 NSCLC 与对照组方面，训练数据集中的 ROC 曲线下面积（AUC）为 0.80（95%CI[0.74-0.85]），验证数据集中的 AUC 为 0.79（95%CI[0.71-0.87]）。早期和晚期 NSCLC 的 AUC 分别为 0.75（95%CI[0.68-0.81]）和 0.86（95%CI[0.82-0.91]）。此外，该模型在鳞癌（AUC=0.90，95%CI[0.85-0.95]）与对照组的分类中表现出更好的性能，而在腺癌（AUC=0.77，95%CI[0.71-0.82]）中表现稍差。涉及甘氨酸、丝氨酸和苏氨酸代谢；丙氨酸、天冬氨酸和谷氨酸代谢；以及精氨酸生物合成的三个重要代谢途径与 AA 谱的改变有关。
中国 NSCLC 患者血清中几种 AA 的水平发生了改变。这些改变的 AA 可能被用于将病例与对照区分开来。甘氨酸、丝氨酸和苏氨酸代谢；丙氨酸、天冬氨酸和谷氨酸代谢和精氨酸生物合成途径可能在 NSCLC 患者的代谢中发挥作用。
