Abstract
As an important biomarker for cancer, polyamine levels in body fluid could be employed for monitoring the colorectal cancer (CRC), however the role of polyamines in the development and therapeutics phases of CRC remains uncertain. In this paper, the relationship between polyamines and CRC development and therapeutics had been investigated by the study of changes in plasma polyamine levels during the precancerous, developmental and treatment phases of CRC. After inducing CRC in Wistar rats by intraperitoneal injection of 1, 2-dimethylhydrazine, the animals were given a traditional Chinese medicine, Aidi injections. Firstly, the polyamine levels in the plasma of CRC, healthy and medicated rats were measured by UHPLC-MS/MS assay. In addition, Lasso regression analysis was used for screening and confirming the key markers, which can be employed for distinguishing the healthy and CRC rats as well as the CRC and medication rats. The results obtained showed that polyamine metabolism had been disrupted by CRC but returned to normal levels following Aidi injections and, in particular, putrescine and agmatine were closely correlated with CRC. Our results demonstrate the potential value of plasma polyamine metabolic profiling during the early diagnosis and medical treatment of CRC. Also, the integrated method of polyamine metabolite target analysis and lasso regression analysis can be applied in metabolomics for seeking the differential metabolites.
Highlights
According to a report by the National Cancer Institute, colorectal cancer (CRC) is one of the most common cancers in the world
The CRC group rats were induced with DMH for 20 weeks, and the histopathology of each rat rectum was examined on 4th, 8th, 12th, 16th and 20th weeks after DMH induction (Figure 1) From the histopathology of the carcinogenic process induced by DMH, it was concluded that CRC developed from mucosal hyperplasia to invasive carcinoma during our experiment
Studies of polyamine metabolic profiling during cancer development and therapy are rare and, here, we have presented a detailed and systematic analysis of plasma polyamine metabolic profiles in CRC
Summary
According to a report by the National Cancer Institute, colorectal cancer (CRC) is one of the most common cancers in the world. The systematic study of polyamine metabolic profiles may provide important information for cancer monitoring during its initial stages and allow prediction of the therapeutic effects of anti-cancer drugs. As endogenous substances take part in most life activity, polyamines are more likely to be affected by traditional Chinese medicine (TCM), which can play its therapeutic effect by overall treatment with multitarget and multi-channel. Altered polyamines and their metabolic profiles could help us better understand the mechanism of TCM action and improve its effects during cancer therapy
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