Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review

Abstract

Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.

Keywords: amino acids; breast cancer; gynecological cancers; metabolomics; proline.

Figure 1

The different levels of “omics” research.

Figure 2

Estimated percentage of new cancer cases (a) and cancer deaths (b) worldwide for 2020 [8].

Figure 3

Search terms and strategy.

Figure 4

Algorithm of the literature search for reviewed articles.

Figure 5

The overview on proline metabolism in gynecological cancers. Numbers represent enzymes involved in proline-relation reactions: 1—glutamate dehydrogenase; 2—P5C dehydrogenase; 3—P5C synthase; 4—glutamine synthase; 5—glutaminase; 6—ornithine aminotransferase; 7—proline dehydrogenase/oxidase; 8—P5C reductase; 9—prolidase; TCA, tricarboxylic acid. α-KG—alpha ketoglutarate; Glu—glutamic acid; Gln—glutamine; Gly—glycine; Orn—ornithine; P5C—pyrroline-5-carboxylate; Pro—proline. Created with Biorender.com accessed on 13 July 2021.