Methylated Septin9 has moderate diagnostic value in colorectal cancer detection in Chinese population: a multicenter study.

BACKGROUND: The detection rate of methylated Septin9 (mSEPT9) in colorectal cancer (CRC) is varied greatly across the studies. This study aimed to evaluate the diagnostic ability of mSEPT9 in CRC, and compare the diagnostic efficacy with fecal immunochemical test (FIT). METHODS: 326 subjects from four centers were prospectively recruited, including 179 CRC and 147 non-CRC subjects. The plasma was collected for mSEPT9 and CEA, AFP, CA125, CA153 and CA199 test, and fecal samples for FIT tests. Sensitivity, specificity and area under the curve (AUC) of receiver operating characteristic curve were calculated to evaluate the diagnostic value of each biomarker. RESULTS: The positive rate in mSEPT9 and FIT, and the level of CEA, CA125 and CA199 were significantly higher in CRC compared with non-CRC subjects. The mSEPT9 positive rate was not associated with TNM stage and tumor stage. The sensitivity, specificity and AUC of mSEPT9 in diagnostic CRC were 0.77, 0.88 and 0.82, respectively, while the value in FIT was 0.88, 0.80 and 0.83, respectively. mSEPT9 and FIT have higher AUC value than that of CEA, CA125 and CA199. Combination of both mSEPT9 and FIT positive increased sensitivity and AUC to 0.98 and 0.83, respectively, but the specificity was declined. mSEPT9 has a slightly low sensitivity in diagnosis of colon cancer (0.87) compared with rectal cancer (0.93). CONCLUSION: mSEPT9 demonstrated moderate diagnostic value in CRC detection, which was similar to the FIT but superior to the CEA, CA125 and CA199. Combination of mSEPT9 and FIT further improved diagnostic sensitivity in CRC. TRIAL REGISTRATION: ChiCTR2000038319.

Endothelin-3 growth factor levels decreased in cervical cancer compared with normal cervical epithelial cells.

We used cDNA microarray analysis of RNA extracted from normal, dysplastic, and cancerous cervical tissues to identify the changes in gene expression during the procession from normal to cancerous cervical epithelial cells. We found the expression of 5 genes in cancerous cervical epithelial cells that were not found in normal cervical epithelial cells, among which were lymphoid-restricted membrane protein, protease serine 2, WD repeat domain 59, thyrotropin-releasing hormone degrading enzyme, and the endothelin-3 growth factor. We then analyzed the expression levels of endothelin growth factors 1, 2, and 3 (ET-1, ET-2, and ET-3) and their receptors A and B (ETR-A and ETR-B) by reverse transcriptase-polymerase chain reaction in 3 cervical cancer cell lines and by immunohistochemical staining in cervical normal, dysplastic, and cancer tissues. ET-1, ET-2, and ET-3 growth factor levels were detectable in the maturing layer of cervical epithelium but not in the germinal layer. All 3 growth factors (ET-1, ET-2, and ET-3) were detected in the cytoplasm of the maturing normal cervical epithelial cells. In addition, there were decreased levels of ET-3 and increased levels of ET-1, ET-2, ETR-A, and ETR-B in cancerous cervical epithelial cells compared with normal cervical epithelial cells. These results suggest that the reduction of ET-3 growth factor levels may be important in the transition from normal to cancerous cervical epithelium.