Clinical correlation of plasma amino acid profile of post-surgical gastric cancer patients and metastatic gastric cancer patients for establishing biomarker of metastasis

Abstract

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.