CRC is one of the most common malignant tumors of the digestive system. The occurrence and development of CRC is a multi-factor and multi-gene cooperative process . Therefore, it is of great significance to identify the factors that change in the occurrence and development of colorectal cancer for inhibiting tumor growth. Through analysis, we found that the levels of Ala, Pro, and Val were significantly different in different TNM stages, and serum Ala, Pro, Val were negatively correlated with TNM stages. The higher the TNM stage, the lower the serum Ala, Pro, and Val levels.
During periods of cellular stress, cancer cells alter their metabolism to increase survival, undergo uncontrolled proliferation, and progress toward metastasis formation . Amino acids serve as substrates for protein synthesis and energy sources for protein production and metabolism, regulating many cellular functions. Studies have shown that alanine supply supports metabolism, growth, and treatment resistance in pancreatic ductal adenocarcinoma (PDAC) . Furthermore, PDAC cells need to meet their increased alanine requirements by upregulating SLC38A2. Alanine-deficient cancer cells experience a severe metabolic crisis that results in significantly impaired tumor growth.
The proliferation of cancer cells is dependent on biomass production, the biosynthesis of macromolecules such as DNA and proteins from amino acids and other metabolites, proline, which has been shown to promote the production of proteins, which are responsible for cell proliferation. Required [14, 15]. Proline is synthesized from ornithine or glutamate, and the specific role of proline in metabolic regulation is now accepted [16–18], and recent work not only suggests that proline metabolism is critical in cancer reprogramming [15, 19, 20], and its clinical significance has also been established . In human gastrointestinal and kidney tumors, immunohistochemistry showed that proline oxidase levels were significantly reduced in nearly 80% of subjects compared to corresponding normal tissues . Furthermore, proline extracted from collagen has been found to support the proliferation of pancreatic cancer cells . The importance of proline for the proliferation of pancreatic cancer cells is manifested not only in the direct binding of proline to proteins but also in the catabolism of proline leading to the production of glutamine, glutamate, and aspartate . Furthermore, it was found that down-regulation of proline biosynthesis in cancer cells expressing c-MYC resulted in a decrease in glycolysis and ATP production [15, 20]. Interestingly, recent studies have shown increased proline biosynthesis in isocitrate dehydrogenase 1 (IDH1)-mutated cancer cells compared to wild-type IDH cancer cells, which leads to electron transport in the TCA cycle Partial unhooking of the chain . Thus, ATP-coupled oxygen consumption is increased in IDH1-mutated cancer cells under the effect of proline biosynthesis inhibition. Therefore, it is easy to speculate that both of these observations could affect cancer cell proliferation by disturbing cellular redox balance. Taken together, proline metabolism can support cancer proliferation and is, therefore, an interesting point of intervention to inhibit the growth of certain types of tumors.
Studies have shown that the biosynthesis of proline helps maintain intracellular nucleotide levels . In some cancer cells, inhibition of proline biosynthesis was found to impair tumorigenic potential and reduce the growth of attached monolayers [19, 20]. Muscle atrophy and amino acid mobilization in the muscles of cancer patients may be driven by the secretion of different tumor-derived mediators. Therefore, a gradual decrease in muscle mass may be observed in some cancer patients. It has also been reported that the oxidation rate of branched-chain amino acids (BCAAs) in the muscle of cancer patients is higher . There is increasing evidence that BCAAs are essential nutrients for cancer growth and are used by tumors as an energy source .
Molecularly targeted therapy refers to the use of drugs or other substances to target specific molecules (molecular targets) to stop the growth and spread of cancer cells. Identifying ideal targets is the key to the successful development of molecularly targeted therapies for cancer . In this study, 11 amino acids and carnitine metabolites involved in the occurrence and development of CRC were analyzed. Whether they can be the target of targeted therapy? Targeted therapy of CRC with different metabolic pathways still needs more research to verify.
To the best of our knowledge, this study is the first to analyze the differences in the occurrence and development of CRC from the perspective of amino acids and obtained three metabolites with significant differences. More data analysis is needed to explore how the above-mentioned differential metabolites affect the occurrence and development of CRC. Of course, this study also has certain limitations. Since our data are data in the past 3 years, we cannot discuss the survival time and survival rate of patients, so it is difficult for us to understand the survival curve and prognosis of patients. More research is needed in the future to further understand the occurrence and development of CRC.