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血清缬氨酸、甲硫氨酸浓度水平与乳腺癌临床特征及风险的相关性
作者姓名:解思琦  张恒瑀  李红万  谭明建  王青  李思嘉  郑凯  刘德权  唐诗聪
作者单位:云南省肿瘤医院/昆明医科大学第三附属医院乳腺外一科,云南 昆明 650118
基金项目:国家自然科学基金资助项目 (81960542,81960517);云南省教育厅科学研究基金资助项目 (2019J1288,2020J0198);云南省科技厅科技计划基础研究专项基金资助项目 (202001AU070053,202001AU070093);云南省高层次卫生计生技术人才培养基金资助项目 (H-2019075)
摘    要:  目的  比较健康人群、乳腺良性肿瘤患者和乳腺癌患者的血清Val、Met浓度差异,探究血清缬氨酸和甲硫氨酸与乳腺癌临床特征及风险的关系。  方法  采用液相色谱-串联质谱法测定38名乳腺良性肿瘤患者,87名乳腺癌患者的血清Val、Met浓度,同时选择91名健康人群作为对照组。经Kruskal-Wallis H检验比较不同分组间的血清Val、Met浓度差异,分析不同化疗方案及手术方式对乳腺癌患者血清Val、Met浓度的影响。再通过二元Logistic回归分析、计算优势比和95%置信区间(CI)来评估血清Val、Met与乳腺癌的风险关系并绘制ROC曲线评估血清Val及Met对乳腺癌的诊断效能。  结果  与健康对照组相比,乳腺癌(BC)组的血清Val浓度水平高于乳腺良性肿瘤(BE)组和健康对照组,BC组和BE组的Met水平都高于健康对照组,差异有统计学意义(P < 0.05)。不同TNM分期及接受不同化疗方案的乳腺癌患者血清Val、Met浓度,差异无统计学意义(P > 0.05),但不同分子分型组间乳腺癌患者的血清Val浓度,差异有统计学意义(P < 0.05)。另外,血清Val浓度水平和乳腺癌风险无明显关系,但血清Met会显著影响乳腺癌的发生(P < 0.001),血清Met的浓度越高,乳腺癌的患病风险就越高,并且Met的浓度水平每增加一个单位,乳腺癌患病风险就增加24%(OR = 1.24 95% CI:1.15~1.34)。并且血清Met(P < 0.001)对乳腺癌的诊断具有统计学意义。其AUC为0.83、敏感度及特异性分别为69%和90.1%,临界值为19.76 μmol/L。  结论  乳腺癌患者的血清Val浓度高于乳腺良性肿瘤患者及健康人群;与健康人群相比,乳腺癌患者及乳腺良性肿瘤患者的血清Met浓度水平也有所升高。血清Val浓度水平和乳腺癌风险无明显关系,但血清Met与乳腺癌风险呈负相关,并且血清Met对乳腺癌诊断具有一定的诊断效能。

关 键 词:氨基酸    缬氨酸    甲硫氨酸    乳腺癌    乳腺良性肿瘤
收稿时间:2022-03-05

Correlation between Serum Valine and Methionine Levels and Clinical Features and Risk of Breast Cancer
Affiliation:Dept. of Breast Surgery,The 3rd Affiliated Hospital,Kunming Medical University/ Yunnan Cancer Hospital,Kunming Yunnan 650118,China
Abstract:  Objective  To compare the differences in serum Val and Met concentrations in healthy people, patients with benign breast tumors and breast cancer patients, and explore the relationship between serum valine and methionine and the clinical characteristics and risk of breast cancer.   Methods   The serum Val and Met concentrations of 38 patients with benign breast tumors and 87 patients with breast cancer were determined by liquid chromatography-tandem mass spectrometry, and 91 healthy participants were selected as the control group. The Kruskal-Wallis H-test was used to compare the differences in serum Val and Met concentrations between different groups, and the effects of different chemotherapy regimens and surgical methods on serum Val and Met concentrations in breast cancer patients were analyzed. Binary Logistic regression analysis, calculation of odds ratio and 95% confidence interval (CI) were used to evaluate the relationship between serum Val, Met and breast cancer risk, and ROC curve was drawn to evaluate the diagnostic performance of serum Val and Met for breast cancer.   Results   Compared with healthy control group, the serum Val concentration in breast cancer (BC) group was higher than that in benign breast tumor (BE) group and healthy control group, and the Met level in BC and BE groups was higher than that in healthy control group, and the differences were statistically significant (P < 0.05). There were no significant differences in serum Val and Met concentrations among breast cancer patients with different TNM stages and chemotherapy regimens, but there were differences in serum Val concentrations among breast cancer patients with different molecular types. In addition, there was no significant relationship between serum Val concentration level and breast cancer risk, but serum Met significantly affected the occurrence of breast cancer (P < 0.001). The higher serum Met concentration was, the higher the risk of breast cancer was; and for every one-unit increase in Met levels, the risk of breast cancer increased by 24 percent (OR = 1.24 95%CI: 1.15-1.34). Serum Met (P < 0.001) was statistically significant in the diagnosis of breast cancer. The AUC was 0.83, the sensitivity and specificity were 69% and 90.1%, respectively, and the critical value was 19.76 μmol/L.   Conclusion  The serum Val concentration of breast cancer patients was higher than that of benign breast tumor patients and healthy population. Serum Met levels were also elevated in patients with breast cancer and benign breast tumors compared with healthy subjects. There was no significant correlation between serum Val concentration and breast cancer risk, but serum Met was negatively correlated with breast cancer risk, and serum Met had certain diagnostic efficacy for breast cancer diagnosis.
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