Using an alternative higher specificity rule (2/3 analysis), according to the manufacturer��s suggestion, we observed a specificity of 98.9%. Only 1% (1/92) of the NED group was SEPT9 positive, so this method is more suitable to detect the NED samples correctly as healthy compared with 1/3 analysis. Applying this rule to the CRC cases, 73 samples or 79.3% showed SEPT9 positivity, a level of sensitivity http://www.selleckchem.com/products/XL184.html that outperforms gFOBT and CEA for the detection of CRC. The selection of a higher sensitivity or higher specificity algorithm may be driven by differing objectives of screening programs. In this study, we also compared the sensitivity of methylated Septin 9 as a serum biomarker for both left- and right-sided CRC to gFOBT and CEA serum level.
Recent studies have demonstrated differences in the molecular patterns of colorectal carcinogenesis based on factors such as age, gender, and tumor localization [27]�C[30]. The elevated number of diagnosed left-sided colon cancers may be due to anatomical factors such as the lower colonic lumen diameter. Ghazi et al. found that left-sided CRC tended to have a lower T stage and higher N stage. However, they found no significant difference in the number of involved lymph nodes between the colonic locations. In addition, right-sided CRC has a worse prognosis than left-sided [31] and Weiss et al. found a higher mortality rate in right-sided stage III CRC [32]. While right-sided tumors display elevated gene expression levels of cell cycle control and Wnt signaling genes, left-sided colon cancers show reduced expression of tumor suppressor genes and cytokeratin 20 and elevated expression of COX-1 and genes that promote stromal expansion [33], [34].
Furthermore, difference in tumorigenesis between left- and right-sided colon cancers may be caused by epigenetic factors, as shown by differences in methylation. In regard to DNA methylation, it is known that some right-sided (CIMP) colon cancers have more frequent alterations as compared to left-sided cancers. Left-sided colon cancers can display a mutator phenotype, while right-sided tumors display as hypermethylator phenotype [35]�C[37]. Taken together, it is of significant clinical importance that screening methods for CRC are reliable for both left- and right-sided CRC. CRC detection by gFOBT in the context of left and right side of the colon has been evaluated in previous studies.
Steele et al. found gFOBT to be less sensitive for Carfilzomib both rectal cancer and right-sided cancer of the colon [38]. In our study, more left-sided CRC (83%) cases were detected by gFOBT than right-sided CRCs (50%) as well. The reason for detecting more left sided CRC may be explained by the localization of the disease and, due to stool consistency, blood originating from left-sided cancers may appear earlier in the feces.