Plasma-free amino acid profiling of cervical cancer and cervical intraepithelial neoplasia patients and its application for early detection

Abstract

In this study, plasma-free amino acid profiles were used to investigate pre-cancerous cervical intraepithelial neoplasia (CIN) and cervical squamous cell carcinoma (CSCC) metabolic signatures in plasma. Additionally, the diagnostic potential of these profiles was assessed, as well as their ability to provide novel insight into CSCC metabolism and systemic effects. Plasma samples from CIN patients (n = 26), CSCC patients (n = 22), and a control healthy group (n = 35) were analyzed by high-performance liquid chromatography, and their spectral profiles were subjected to the t test for statistical significance. Potential metabolic biomarkers were identified using database comparisons that examine the significance of metabolites. Compared with healthy controls, patients with CIN and CSCC demonstrated lower levels of plasma amino acids; plasma levels of arginine and threonine were increased in CIN patients but were decreased in cervical cancer patients. Additionally, the levels of a larger group of amino acids (aspartate, glutamate, asparagine, serine, glycine, histidine, taurine, tyrosine, valine, methionine, lysine, isoleucine, leucine, and phenylalanine) were gradually reduced from CIN to invasive cancer. These findings suggest that plasma-free amino acid profiling has great potential for improving cancer screening and diagnosis and for understanding disease pathogenesis. Plasma-free amino acid profiles may have the potential be used to determine cancer diagnoses in the early stage from a single blood sample and may enhance our understanding of its mechanisms.

Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

“…Decreases in plasma arginine concentrations occur in cervical cancer and renal cell carcinoma patients. 43,44 Physiological compensation through protein breakdown, contributing to cancer induced cachexia, and arginine recycling by the intestinal-renal axis may try to compensate for lowered arginine levels. 45 Because arginine is essential for proliferation and maintenance of AML viability, arginine starvation by the PEG recombinant arginase BCT-100 should be cytotoxic to AML, as in other tumor types.…”

Perioperative dynamics and significance of amino acid profiles in patients with cancer

“…These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and for understanding disease pathogenesis. In addition, other studies have revealed correlation between PFAA profiles and clinicopathological characteristics such as pathological grading, lymph node metastasis and clinical stage of patients with esophageal squamous cell carcinoma [ 16 ] and cervical cancer [ 32 ]. The longitudinal studies with larger sample sizes and longer follow up are needed to further justify whether PFAA might predict prognosis.…”

Plasma-free amino acid profiles are predictors of cancer and diabetes development

“…59 As summarized in Table 1, Gly consumption was pronounced in pancreatic cancer, 27 breast cancer, 28, 29 colorectal cancer 41 and cervical cancer. 42 While Ser levels were high in some patients with pancreatic cancer, 20 breast cancer, 31, 32 lung cancer, and colorectal cancer, 29 probably due to the overexpression of phosphoglycerate dehydrogenase, other cancers, such as colorectal cancer, 21, 27, 42 pancreatic cancer, 27 gastric cancer 28 and cervical cancer 43 consumed Ser. Although Ser and Gly could be inter-converted and either of them might be used for one-carbon metabolism and nucleotide synthesis, convincing evidence suggested that cancer cell proliferation were supported by Ser instead of Gly consumption.…”