Role of Urinary Biomarkers in the Diagnosis of Adenoma and Colorectal Cancer: A Systematic Review and Meta-Analysis

Abstract

The growing interest in enhancing and spreading colorectal cancer (CRC) screening has been stimulating the exploration of novel biomarkers with greater sensitivity and specificity than immunochemical faecal occult blood test (iFOBT). The present study provides i) a systematic review of the urinary biomarkers that have been tested to achieve early CRC diagnosis and assess the risk of colorectal adenoma and adenocarcinoma, and ii) a meta-analysis of the data regarding the urinary prostaglandin (PG) metabolite PGE-M.As regard to gene markers, we found significantly different percent methylation of the vimentin gene in CRC patients and healthy controls (HC) (p<0.0001). Respect to metabolism of nitrogenous bases, cytidine, 1-methyladenosine, and adenosine, have higher concentrations in CRC patients than in HC (respectively, p<0.01, p=0.01, and p<0.01). As regard to spermine we found that N1,N12 diacetyl spermine (DiAcSpm) and N1, N8 diacetylspermidine (DiAcSpd) were significantly higher in CRC than in HC (respectively p=0.01 and p<0.01). Respect to PGE-M, levels were higher in CRC than in those with multiple polyposis (p<0.006) and HC subjects (p<0.0004). PGE-M seems to be the most interesting and promising urinary marker for CRC and adenoma risk assessment and for CRC screening.In conclusion, evidence suggests that urinary biomarker could have a potential role as urinary biomarkers in the diagnosis of colorectal cancer. Particularly, PGE-M seems to be the most promising urinary marker for CRC early detection.

Colorectal cancer: epigenetic alterations and their clinical implications

“…Promoter DNA hypermethylation of specific CRC driver genes may be identified in tools, urine and blood as diagnostic biomarkers and some of them are already available for clinical use. Some examples of these genes are MLH1, CDKN2A, MGMT, among others that have been identified in human stools sample in several studies (76); VIM, WIF1, ALX4 and NDRG4 have been detected in urine (77) and MLH1, APC, MGMT, RASSF2A and TMEFF2 among others in blood samples. Investigating the methylation status of circulating DNA, some of them (SEPT9, ALX4, SDC2, RUNX3, TMEFF2, NEUROG1) present high sensitivity and specificity for CRC detection during initial stages (78).…”

Associations of branched-chain amino acids with parameters of energy balance and survival in colorectal cancer patients: results from the ColoCare study

“…A particular strength of this study is that urinary biomarkers can be assessed using a non-invasive approach for continuous disease monitoring. (Altobelli et al 2016)…”

Gene polymorphisms of SFTPB rs7316, rs9752 and PAOX rs1046175 affect the diagnostic value of plasma Pro‐SFTPB and DAS in Chinese Han non–small‐cell lung cancer patients

“…N1,N12‐diacetylspermine (DAS), involved in the regulation of key metabolic enzymes in normal and cancer cells, is a minor polyamine component of human urine. Clinical studies found that DAS levels can perform as predictors of tumor aggressiveness for early diagnosis of tumors such as NSCLC, breast cancer, and colorectal cancer (CRC) …”

“…Clinical studies found that DAS levels can perform as predictors of tumor aggressiveness for early diagnosis of tumors such as NSCLC, 8,9 breast cancer, 10 and colorectal cancer (CRC). 11 However, genes encoding pro-SFTPB have genetic polymorphisms at certain locus, and it is still unclear how these loci affect the early diagnosis of NSCLC. Pro-SFTPB is encoded by the SFTPB gene, and the genetic diversity of SFTPB has impact on the occurrence of disease.…”