Certain microorganisms reach a relatively stable abundance or composition when cancer progresses to an advanced stage, supporting their role in cancer progression. The phyla Bacteroides, Firmicutes and Proteobacteria were found to be abundant in patients with CRC compared with healthy individuals. In a previous study, the contribution of gut microbiota to the development and progression of CRC was examined using macro-genomic analysis ( 9). Such alterations may cause ecological dysbiosis, an imbalance in microbial composition that disturbs the host-microbiota interactions and may drive the development of CRC. Alterations in the intestinal microecosystem have been identified as a key factor influencing the development of CRC ( 8). A previous study has shown that the gut microbiota has a significant impact on human health and disease ( 7). For instance, long-term alcohol abuse may cause damage to the intestinal mucosa and increase the risk of colorectal cancer ( 6). In addition, certain environmental factors, such as smoking, obesity, sedentary lifestyle and exposure to certain chemicals or toxins, have also been associated with an increased risk of CRC development. For instance, mutations in genes such as APC, TP53 and KRAS have been implicated in increasing the risk of CRC ( 5).
CRC is thought to be triggered by various factors, including genetic predisposition. Overall, <20% of patients diagnosed with advanced CRC survive beyond 5 years ( 4). However, the majority of patients present with advanced disease and have a poor prognosis, and even with surgery the recurrence rate remains high. Therefore, early detection and surgery are critical in controlling this disease. CRC development often follows the adenoma-carcinoma sequence, a process that can take several years. The majority of CRCs arise from pre-existing colorectal adenomas (CRAs) ( 3). In 2020, there were an estimated 1.9 million new cases of CRC worldwide, leading to ~935,000 deaths globally ( 2). In conclusion, the present study provided preliminary insight into the metabolic changes associated with CRC and may have important implications for the development of future diagnostic and treatment strategies.Ĭolorectal cancer (CRC) is a significant global health concern, accounting for ~10% of all new cancer cases worldwide and ranking as the second leading cause of cancer-related mortality ( 1). The analysis of the current study also showed that the expression of metabolites involved in ‘sphingolipid metabolism’ was mainly dysregulated in LTS and STS, while N-acetylmannosamine and 2,5-dihydroxybenzaldehyde were associated with better overall survival. Joint quantification of these three metabolites resulted in an area under the ROC curve of 0.969 in the diagnosis of CRC. ROC analysis found that 9,10-dihydroxy-12-octadecenoic acid, cholesterol ester (18:2) and lipoxinA4 distinguished CRC from HC.
The results of the current study showed that the enriched pathways in CRC included ‘caffeine metabolism’, ‘thiamine metabolism’, ‘phenylalanine, tyrosine and tryptophan biosynthesis’ and ‘phenylalanine metabolism’. The association of gut metabolites with survival in patients with CRC was also analyzed by comparing short-term survivors (STS) and long-term survivors (LTS), and the prognostic ability of metabolites was predicted using Cox regression and Kaplan-Meier analysis. Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic utility for distinguishing CRC from HC. Using orthogonal partial least squares discriminant analysis, metabolomic features distinguishing the three groups were identified. In the present study, targeted metabolomic analysis was conducted on fecal samples from 35 patients with CRC, 37 patients with colorectal adenoma and 30 healthy controls (HC) to identify metabolite biomarkers. Despite extensive research, the precise role of gut metabolites in CRC development and clinical outcomes remains unclear, while its elucidation may aid the development of improved clinical diagnosis and treatment options. Colorectal cancer (CRC) is one of the leading global malignancies with low 5-year survival and high mortality rates.
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