Sun Yang, Gan Mingyue, Wu Yongyan, Gao Wei, Lu Yan
Department of Otolaryngology Head and Neck Surgery,First Affiliated Hospital of Jinzhou Medical University,Jinzhou,121000,China.
Department of Otolaryngology Head and Neck Surgery,Shenzhen Institute of Otorhinolaryngology.
Lin Chuang Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2024 Aug;38(8):715-721. doi: 10.13201/j.issn.2096-7993.2024.08.008.
To detect the differences in types and levels of amino acids in the peripheral serum of patients with laryngeal squamous cell carcinoma and non-tumor patients, and explore their relationship with clinical parameters of laryngeal squamous cell carcinoma as well as their clinical value in diagnosis. High-performance liquid chromatography-tandem mass spectrometry(HPLC-MS) was employed to detect the serum amino acid contents and levels of 62 patients diagnosed with laryngeal carcinoma and 141 non-tumor patients at the First Affiliated Hospital of Jinzhou Medical University between September 2018 and February 2021. The study compared the differences in 22 non-essential and essential amino acids found in the serum between the experimental group and the control group. An ROC curve and risk scoring formula of multivariate linear logic regression model was utilized to evaluate the efficiency of serum amino acids in the early diagnosis of laryngeal carcinoma. There were significant differences in the contents of fourteen types of amino acids between the experimental and control groups, with thirteen amino acids showing higher levels in the experimental group(<0.05). Seven of these amino acids were essential, including phenylalanine, threonine, leucine, valine, histidine, tyrosine, and citrulline. The other six amino acids were non-essential, including arginine, asparagine, cysteine, glycine, ornithine, and proline. Interestingly, the content of homocysteine in the experimental group was lower than that in the control group(=0.024). Further analysis showed that patients with laryngeal squamous cell carcinoma in TNM stage Ⅰ and Ⅱ had higher serum methionine levels compared to those in stages Ⅲ and Ⅳ(=0.026). In addition, the content of serum histidine was higher in patients with poorly differentiated squamous cell carcinoma compared to those with well-differentiated squamous cell carcinoma(=0.041). The level of asparagine in the serum of patients with laryngeal squamous cell carcinoma older than 64 years old was lower than that in patients younger than 64 years old(=0.033). The level of tryptophan in the serum of patients with a smoking history was lower than that in patients without a smoking history(=0.033). The level of citrulline in the serum of patients with a history of alcohol consumption was higher than that in patients with no history of alcohol consumption(=0.003). ROC curve analysis showed that out of the 14 different amino acids between the experimental and control groups, citrulline and cysteine were relatively effective as independent factors in the diagnosis of laryngeal squamous cell carcinoma, with an AUC of 0.856 and 0.850, respectively. Arginine was the most sensitive factor in the diagnosis of laryngeal squamous cell carcinoma(AUC=0.855). However, citrulline alone had the highest specificity(0.830) in the diagnosis of laryngeal squamous cell carcinoma, and the combination of 12 amino acids significantly improved the diagnostic efficiency of laryngeal squamous cell carcinoma, with an AUC of 0.946, sensitivity of 0.887, and specificity of 0.894. A risk score formula for a multivariate logistic regression model was established based on the differential amino acid content in the serum. The risk score of laryngeal squamous cell carcinoma group was higher than that of the non-tumor group(<0.001). The AUC of risk score in the diagnosis of laryngeal squamous cell carcinoma was 0.953 with sensitivity and specificity of 0.957 and 0.855. This study found that there are differences in the contents of 14 amino acids among which 13 amino acids were increased in serum of patients with laryngeal squamous cell carcinoma, and were associated with age, clinical stage, pathological differentiation, smoking, and drinking. Combined detection of 12 amino acids can improve the diagnostic efficiency of laryngeal squamous cell carcinoma and serve as potential markers for the auxiliary diagnosis of laryngeal squamous cell carcinoma using peripheral blood samples. Additionally, the established risk score model was found to be more effective in the diagnosis of laryngeal squamous cell carcinoma, indicating its important potential value as an auxiliary diagnostic tool.
检测喉鳞状细胞癌患者与非肿瘤患者外周血清中氨基酸的种类和水平差异,探讨其与喉鳞状细胞癌临床参数的关系及其诊断的临床价值。采用高效液相色谱 - 串联质谱法(HPLC - MS)检测锦州医科大学附属第一医院2018年9月至2021年2月期间诊断的62例喉癌患者和141例非肿瘤患者的血清氨基酸含量和水平。该研究比较了实验组和对照组血清中22种非必需氨基酸和必需氨基酸的差异。利用多因素线性逻辑回归模型的ROC曲线和风险评分公式评估血清氨基酸在喉癌早期诊断中的效率。实验组和对照组之间14种氨基酸的含量存在显著差异,其中13种氨基酸在实验组中水平较高(<0.05)。这些氨基酸中有7种是必需氨基酸,包括苯丙氨酸、苏氨酸、亮氨酸、缬氨酸、组氨酸、酪氨酸和瓜氨酸。另外6种氨基酸是非必需氨基酸,包括精氨酸、天冬酰胺、半胱氨酸、甘氨酸、鸟氨酸和脯氨酸。有趣的是,实验组中同型半胱氨酸的含量低于对照组(=0.024)。进一步分析表明,TNM分期为Ⅰ期和Ⅱ期的喉鳞状细胞癌患者血清蛋氨酸水平高于Ⅲ期和Ⅳ期患者(=0.026)。此外,低分化鳞状细胞癌患者血清组氨酸含量高于高分化鳞状细胞癌患者(=0.041)。64岁以上喉鳞状细胞癌患者血清中天冬酰胺水平低于64岁以下患者(=0.033)。有吸烟史患者血清中色氨酸水平低于无吸烟史患者(=0.033)。有饮酒史患者血清中瓜氨酸水平高于无饮酒史患者(=0.003)。ROC曲线分析表明,实验组和对照组之间14种不同氨基酸中,瓜氨酸和半胱氨酸作为喉鳞状细胞癌诊断的独立因素相对有效,AUC分别为0.856和0.850。精氨酸是喉鳞状细胞癌诊断中最敏感的因素(AUC = 0.855)。然而,单独瓜氨酸在喉鳞状细胞癌诊断中具有最高的特异性(0.830),12种氨基酸联合检测显著提高了喉鳞状细胞癌的诊断效率,AUC为0.946,敏感性为0.887,特异性为0.894。基于血清中差异氨基酸含量建立了多因素逻辑回归模型的风险评分公式。喉鳞状细胞癌组的风险评分高于非肿瘤组(<0.001)。风险评分在喉鳞状细胞癌诊断中的AUC为0.953,敏感性和特异性分别为0.957和0.855。本研究发现,14种氨基酸含量存在差异,其中13种氨基酸在喉鳞状细胞癌患者血清中升高,且与年龄、临床分期、病理分化、吸烟和饮酒有关。12种氨基酸联合检测可提高喉鳞状细胞癌的诊断效率,可作为利用外周血样本辅助诊断喉鳞状细胞癌的潜在标志物。此外,建立的风险评分模型在喉鳞状细胞癌诊断中更有效,表明其作为辅助诊断工具具有重要的潜在价值。