胃癌术后患者血浆氨基酸谱与转移性胃癌患者建立转移生物标志物的临床相关性

Samim Akhtar, Zhenhuan Wang, A. Chaturbedi, Xiaoyu Wang, F. Sun
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引用次数: 0

摘要

目的:探讨无转移(胃切除术后早期胃癌)和有转移(晚期胃癌)的胃癌患者血浆游离氨基酸的变化。比较术后胃癌(M0)患者与转移性胃癌(M1)患者的氨基酸水平,寻找预测胃癌转移的生物标志物。对患者生命体征、呼吸频率、脉搏率、血压、体温、疾病分期、主诉、并发症、生存曲线在转移和非转移领域进行临床相关性分析。背景:大多数癌症患者是在转移细胞转移到邻近器官和远处部位后被诊断出来的。在这一点上,治疗是姑息性和支持性的。癌细胞的增殖和肿瘤微环境在胃癌的发生中起着至关重要的作用。基因改变从核苷酸到氨基酸,再到蛋白质,最后形成肿瘤是胃癌发病的自然顺序。利用血浆游离氨基酸谱预测转移可能具有重要意义,因为它将有助于为患者量身定制特定的癌症治疗。血浆氨基酸具有价格合理、价格低廉、使用方便等特点,是预测肿瘤转移的理想工具。方法:本研究共纳入54例患者,其中27例发生胃癌转移,27例早期行胃手术,研究时未复发。研究了23种氨基酸。进行学生t检验,以找出氨基酸的统计显著值。p值≤0.05认为有统计学意义。对p值显著的氨基酸进行多因素logistic回归分析。偏最小二乘判别分析(PLS DA)采用Microsoft SPSS 23版软件®进行。估计投影的可变重要性(VIP),值≥1被认为具有统计学意义。结果:M0组与M1组的表现评分(PS) (p= 0.004)、身体质量指数(BMI) (p= 0.035)差异均有统计学意义。分期(I、II vs. III、IV)差异有统计学意义(p< 0.001)。在第一个月的评价中,M0和M1之间有7种氨基酸,Asp、Cys、Hcy、His、Leu、Orn和Ser显著。6个月评价时,M0和M1之间的8种氨基酸(Cys、Hcy、His、Leu、Met、Thr、Trp和Tyr)差异显著。PLS - DA回归分析、VIP检验显示,Cys、Ser、Hcy、Thr、His、Met、Tyr、Trp是较重要的显著性氨基酸。Kaplan Meier总生存期(OS) = 34.979个月。M0组平均生存时间为43.53±1.741个月。M1患者的平均生存期为26.29±2.635个月。结论:BMI和PS是界定和判断胃癌患者病情的最重要变量。从医生的角度来看,营养和身体活动是疾病结果的重要特征。本研究表明氨基酸在胃癌患者的转移中具有重要的预测和预后意义。
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Clinical correlation of plasma amino acid profile of post-surgical gastric cancer patients and metastatic gastric cancer patients for establishing biomarker of metastasis
Objectives: This research is aimed to evaluate plasma free amino acid in gastric cancer patients without metastasis (early gastric cancer post gastrectomy) and with metastasis (advanced gastric cancer). Amino acids level of postoperative gastric cancer (M0) patients are compared with metastatic gastric cancer (M1) patients in search of biomarker which can predict the metastasis of gastric cancer. We have made clinical correlation of patients’ vital signs, respiratory rate, pulse rate, blood pressure, body temperature, disease stages, chief complaints, complications and survival curve within light of metastatic and nonmetastatic domain. Background: Majority of cancer patients are diagnosed after seeding of metastatic cells to adjacent organs and distant sites. At this point, treatment is palliative and supportive. The cellular propagation of cancer cells and tumor micro-environment plays vital role in genesis of gastric cancer. Genetic alteration leading to faulty nucleotides to amino acids, then to protein, and finally formation of tumor is the natural sequence of pathogenesis of gastric cancer. Prediction of metastasis by use of plasma free amino acid profile may be of great significance because it will help to tailor the patient specific cancer treatment. Plasma Amino acids are ideal for being developed as tool for prediction of metastasis as they are affordable, less expensive and convenient. Method: This study includes total 54 patients, among which 27 had metastasis of Gastric cancer and rest 27 had undergone gastric surgery at early stage with no recurrence at the time of the study. Twenty-three amino acids were studied. Student’s t test was performed to find out statistically significant values of amino acids. The p value of ≤ 0.05 was considered statistically significant. Amino acids with significant p values were investigated with multivariate logistic regression. Partial Least Squares Discriminant Analysis (PLS DA) was done using Microsoft SPSS 23 version software®. Variable Importance of Projection (VIP) was estimated, values ≥ 1 was considered statistically significant. Result: Performance Score (PS) (p= 0.004) and Body Mass Index (BMI) (p= 0.035) were statistically significant between M0 and M1 groups. Staging (I, II vs. III, IV) (p< 0.001) was significant. Seven amino acids, Asp, Cys, Hcy, His, Leu, Orn and Ser were significant between M0 and M1 in first month evaluation. Eight amino acids, Cys, Hcy, His, Leu, Met, Thr, Trp and Tyr were significant between M0 and M1 in sixth month evaluation. PLS DA regression analysis, VIP test showed Cys, Ser, Hcy, Thr, His, Met, Tyr, Trp to be more important amino acids of significance. Kaplan Meier Overall Survival (OS) = 34.979 months. Mean survival time in M0 was 43.53± 1.741 months. Mean survival in M1 was 26.29± 2.635 months. Conclusion: We found BMI and PS as most important variables in defining and determining the disease status of gastric cancer patients. Nutrition and physical activity is very much characteristic of disease outcome from a physician’s perspective. This study propounds amino acids can be valuable biomarkers of predictive and prognostic importance in metastasis in gastric cancer patients.
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