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| 乳腺癌患者血清中20种氨基酸的检测及在乳腺癌筛查中的意义 |
| 何永鹏1,2,郑晓东2,徐灵莉2,雷海科2,林昌海2,付晓琴2,邓浩月1,李沁栖1,任秋宇1,2,朱娟2,甘淋1* |
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(1. 西南医科大学基础医学院生物化学与分子生物学教研室, 泸州 646000;
2. 重庆大学附属肿瘤医院/肿瘤研究所肿瘤转移与个体化诊治转化研究重庆市重点实验室, 重庆 400030
*通信作者) |
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| 摘要: |
| 目的 考察乳腺癌患者与正常体检者血清中氨基酸水平的差异，并探讨其在乳腺癌筛查中的意义。方法 招募2019年4-6月重庆大学附属肿瘤医院病理科确诊的女性乳腺癌患者59例作为乳腺癌组，以正常女性体检者53例作为对照组。采用高效液相色谱-质谱法（HPLC-MS）检测招募者血清中20种氨基酸水平，分析乳腺癌组与对照组间、乳腺癌不同分子亚型组间、早期乳腺癌组与晚期乳腺癌组间氨基酸水平的差异。采用ROC曲线对差异血清氨基酸在乳腺癌筛查中的效能进行评估。结果 乳腺癌组血清中丙氨酸（Ala）、天冬酰胺（Asn）、瓜氨酸（Cit）、谷氨酸（Glu）、组氨酸（His）、异亮氨酸（Ile）、亮氨酸（Leu）、赖氨酸（Lys）、鸟氨酸（Orn）、苯丙氨酸（Phe）、脯氨酸（Pro）、苏氨酸（Thr）、酪氨酸（Tyr）、缬氨酸（Val）的水平均高于对照组（P均<0.05），精氨酸（Arg）水平低于对照组（P=0.003）。ROC曲线分析表明，在乳腺癌患者血清中升高的14种氨基酸中，Ala和Pro单独筛查乳腺癌的效能较高，AUC均为0.75；Ile单独筛查乳腺癌时有最高的灵敏度，达0.82；Lys单独筛查乳腺癌时有最高的特异度，达0.94；这14种氨基酸联合检测时能够提高乳腺癌的筛查效能，AUC为0.88，灵敏度为0.69，特异度为0.94。早期乳腺癌（TNM分期Ⅰ期和Ⅱ期）患者血清Val水平高于晚期（TNM分期Ⅲ期和Ⅳ期）患者（P=0.044），其他19种氨基酸水平在早期和晚期乳腺癌患者之间差异均无统计学意义（P均>0.05）。20种血清氨基酸水平在Luminal A型、Luminal B型、三阴性型、人表皮生长因子受体2（HER2）阳性型乳腺癌组间差异均无统计学意义（P均>0.05）。结论 乳腺癌患者血清中15种氨基酸水平与正常体检者相比存在差异，有助于乳腺癌筛查；14种在乳腺癌患者血清中升高的氨基酸的联合检测有利于提高乳腺癌筛查效能，是有潜力的生物学标志物。 |
| 关键词: 乳腺肿瘤 血清 氨基酸类 筛查 高效液相色谱-质谱法 肿瘤生物标记 |
| DOI：10.16781/j.0258-879x.2021.11.1238 |
| 投稿时间：2020-07-26修订日期：2021-05-27 |
| 基金项目:重庆市科学技术局项目（2021MSXM337），重庆市科研机构绩效激励引导专项（cstc2020jxjl130016）. |
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| Determination of 20 serum amino acids in breast cancer patients and its significance in breast cancer screening |
| HE Yong-peng1,2,ZHENG Xiao-dong2,XU Ling-li2,LEI Hai-ke2,LIN Chang-hai2,FU Xiao-qin2,DENG Hao-yue1,LI Qin-xi1,REN Qiu-yu1,2,ZHU Juan2,GAN Lin1* |
(1. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, Sichuan, China;
2. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital/Chongqing Cancer Research Institute, Chongqing 400030, China
*Corresponding author) |
| Abstract: |
| Objective To investigate the difference of serum amino acid levels between breast cancer patients and normal volunteers, and explore its significance in breast cancer screening. Methods Totally 59 breast cancer patients (breast cancer group) diagnosed by the Department of Pathology, Chongqing University Cancer Hospital from Apr. to Jun. 2019 were recruited, and 53 normal healthy women were selected as control group. The levels of 20 amino acids in the sera of recruited people were detected by high performance liquid chromatography-mass spectrometry (HPLC-MS). The differences of amino acid levels were analyzed between breast cancer group and control group, between different molecular subtype groups of breast cancer, and between early and advanced breast cancer groups. Receiver operating characteristic (ROC) curve was used to evaluate the effectiveness of different serum amino acids in breast cancer screening. Results The levels of alanine (Ala), asparagine (Asn), citrulline (Cit), glutamic acid (Glu), histidine (His), isoleucine (Ile), leucine (Leu), lysine (Lys), ornithine (Orn), phenylalanine (Phe), proline (Pro), threonine (Thr), tyrosine (Tyr) and valine (Val) were higher in the breast cancer group than in the control group (all P<0.05). The level of arginine (Arg) was lower in the breast cancer group than in the control group (P=0.003). ROC curve analysis showed that of the 14 amino acids which were elevated in the sera of breast cancer patients, Ala or Pro alone had better performance in screening breast cancer, and the area under curves (AUCs) were both 0.75; Ile alone had the highest sensitivity, with the AUC of 0.79; Lys alone had the highest specificity, with the AUC of 0.94; and the combined detection of the 14 amino acids improved the performance of breast cancer screening, with the AUC of 0.88, sensitivity of 0.69, and specificity of 0.94. The level of serum Val was higher in early breast cancer patients (TNM stageⅠand Ⅱ) than in advanced patients (TNM stageⅢandⅣ) (P=0.044), and there was no significant difference in the levels of other 19 amino acids (all P>0.05). No significant difference was found in the 20 amino acids between Luminal A type, Luminal B type, triple-negative, and human epidermal growth factor receptor 2 (HER2) positive breast cancer groups (all P>0.05). Conclusion The levels of 15 serum amino acids in breast cancer patients are different from those in normal persons, which is helpful for breast cancer screening. The combination detection of 14 elevated serum amino acids in breast cancer patients can improve the screening performance and may serve as potential biomarkers. |
| Key words: breast neoplasms serum amino acids screening high performance liquid chromatography-mass spectrometry tumor biomarkers |
