Colorectal cancer (CRC) is an important cause of morbidity and mortality worldwide, and is difficult to detect in its early stages. Diagnostic and prognostic biomarkers are required, which may also be the basis for improving the targeted therapy for CRC. Sirtuin 6 (SIRT6) is a member of the sirtuin family of gene regulators, which have specific functions in genomic stability, gene transcription and energy metabolism in tumorigenesis. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is a metabolic enzyme which can be deacetylated by sirtuins. In this study, tissue samples from 29 patients with histologically confirmed CRC of varying grade and stage were studied for SIRT6 and NMNAT2 expression by western blotting and reverse transcription-quantitative polymerase chain reaction. Immunohistochemistry was performed for SIRT6 and NMNAT2 expression in 113 paired (CRC and adjacent) tissue sections. SIRT6 protein and mRNA expression levels were significantly reduced in CRC tissues; NMNAT2 protein and mRNA expression levels were significantly increased in CRC tissues (P<0.01). A negative correlation between the expression of SIRT6 and NMNAT2 in CRC tissue samples was identified (r=−0.246, P<0.01). The reduced expression of SIRT6 and increased expression of NMNAT2 were associated with the tumor depth invasion, stage, differentiation grade (SIRT6 only) and the presence of lymph node metastasis (P<0.05). In conclusion, the findings of the present preliminary study demonstrated that the increased expression of NMNAT2 and reduced expression of SIRT6 may be associated with the progression of CRC. The downregulation of SIRT6 may promote the expression of NMNAT2. Further studies are indicated on the role of NMNAT2 and SIRT6 as potential diagnostic and prognostic biomarkers and as targets for therapy in CRC and other malignant tumors.

Colorectal cancer (CRC) is one of the most common cancers all over the world. It is essential to search for more effective diagnostic and therapeutic methods for CRC. Abnormal nicotinamide adenine dinucleotide (NAD) metabolism has been considered as a characteristic of cancer cells. In this study, nicotinamide mononucleotide adenylyl transferases (NMNATs) as well as p53-mediated cancer signaling pathways were investigated in patients with colorectal cancer. The CRC tissues and adjacent normal tissues were obtained from 95 untreated colorectal cancer patients and were stained for expression of nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) and p53. The survival rate was analyzed by the Kaplan-Meier method and the log-rank test. The multivariate Cox proportional hazard regression analysis was conducted as well. Our data demonstrated that expression of NMNAT2 and p53 was significantly higher in CRC tissues, while NMNAT2 expression is in correlation with the invasive depth of tumors and TNM stage. Significant positive correlation was found between the expression of NMNAT2 and the expression of p53. However, NMNAT2 expression was not a statistically significant prognostic factor for overall survival. In conclusion, our results indicated that NMNAT2 might participate in tumorigenesis of CRC in a p53-dependent manner and NMNAT2 expression might be a potential therapeutic target for CRC.

Previous studies used to enumerate circulating tumor cells to predict prognosis and therapeutic effect of colorectal cancer. However, increasing studies have shown that only circulating tumor cells enumeration was not enough to reflect the heterogeneous condition of tumor. In this study, we classified different metastatic-potential circulating tumor cells from colorectal cancer patients and measured FAM172A expression in circulating tumor cells to improve accuracy of clinical diagnosis and treatment of colorectal cancer. Blood samples were collected from 45 primary colorectal cancer patients. Circulating tumor cells were enriched by blood filtration using isolation by size of epithelial tumor cells, and in situ hybridization with RNA method was used to identify and discriminate subgroups of circulating tumor cells. Afterwards, FAM172A expression in individual circulating tumor cells was measured. Three circulating tumor cell subgroups (epithelial/ biophenotypic/mesenchymal circulating tumor cells) were identified using epithelial-mesenchymal transition markers. In our research, mesenchymal circulating tumor cells significantly increased along with tumor progression, development of distant metastasis, and vascular invasion. Furthermore, FAM172A expression rate in mesenchymal circulating tumor cells was significantly higher than that in epithelial circulating tumor cells, which suggested that FAM172A may correlate with malignant degree of tumor. This hypothesis was further verified by FAM172A expression in mesenchymal circulating tumor cells, which was strictly related to tumor aggressiveness factors. Mesenchymal circulating tumor cells and FAM172A detection may predict highrisk stage II colorectal cancer. Our research proved that circulating tumor cells were feasible surrogate samples to detect gene expression and could serve as a predictive biomarker for tumor evaluation.