SEPTIN9-SDC2-VIM methylation signature as a biomarker for the early diagnosis of colorectal cancer.

The accurate detection of colorectal cancer (CRC) at its initial stage can reduce mortality. However, the broad application of endoscopy has been limited due to the invasive procedure and patient noncompliance. Liquid biopsy with subsequent mapping of methylation in specific cell-free DNA (cfDNA) may represent an alternative approach for early diagnosis. In this study, we have developed a minimal-invasive blood-based test for detection of precancerous lesions and early-stage CRC. Using TCGA M450K methylation data, we identified candidate methylation sites with the highest Fold Change (FC) for three genes (SEPTIN9, SDC2 and VIM), which were selected from previous studies. Based on logistic regression models, we developed a 3-gene methylation signature for CRC diagnosis with high accuracy (Sensitivity =0.959, Specificity =1, AUC =0.997). Using independent public databases and data from blood samples, this model has demonstrated superior performance. The AUC was 0.919-1 and 0.905-0.916 in public tissue database for CRC and blood sample data, respectively. Thus, our proposed 3-gene methylation signature has a more reliable performance than other methods. Furthermore, signal enhancement effect of 3-gene methylation signature can improve the accuracy of early diagnosis for CRC, which demonstrates the potential for clinical application.

The lncRNA CRNDE promotes colorectal cancer cell proliferation and chemoresistance via miR-181a-5p-mediated regulation of Wnt/ß-catenin signaling.

BACKGROUND: With more than 600,000 mortalities each year, colorectal cancer (CRC) is the third most commonly diagnosed type of cancer worldwide. Recently, mechanisms involving noncoding RNAs have been implicated in the development of CRC. METHODS: We examined expression levels of lncRNA CRNDE and miR-181a-5p in 64 cases of CRC tissues and cell lines by qRT-PCR. Gain-of-function and loss-of-function assays were performed to examine the effect of CRNDE and miR-181a-5p on proliferation and chemoresistance of CRC cells. Using fluorescence reporter and western blot assays, we also explored the possible mechanisms of CRNDE in CRC cells. RESULTS: In this study, we found that the expression levels of the CRNDE were upregulated in CRC clinical tissue samples. We identified microRNA miR-181a-5p as an inhibitory target of CRNDE. Both CRNDE knockdown and miR-181a-5p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and TCF4 were inhibitory targets of miR-181a-5p, and that Wnt/ß-catenin signaling was inhibited by both CRNDE knockdown and miR-181a-5p overexpression. Significantly, we found that the repression of cell proliferation, the reduction of chemoresistance, and the inhibition of Wnt/ß-catenin signaling induced by CRNDE knockdown would require the increased expression of miR-181a-5p. CONCLUSIONS: Our study demonstrated that the lncRNA CRNDE could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-181a-5p and the activity of Wnt/ß-catenin signaling.

[Clinical experience of percutaneous endoscopic gastrostomy, jejunostomy, duodenostomy in 120 patients].

OBJECTIVE: To report clinical experience of percutaneous endoscopic gastrostomy, duodenostomy, jejunostomy in 120 patients, focusing on its technique and indications. METHODS: One hundred and twenty patients received percutaneous endoscopic gastrostomy, duodenostomy, jejunostomy from May 2001 to April 2004, including 75 percutaneous endoscopic gastrostomy (PEG), 42 percutaneous endoscopic jejunostomy (PEJ), 2 percutaneous endoscopic duodenostomy (PED), 1 direct percutaneous endoscopic jejunostomy (DPEJ). All tubes established by traditional pull technique. RESULTS: The average duration of PEG was (9 +/- 4) min, PEJ (17 +/- 6) min, DPEJ 20 min, and PED was 10 and 12 min for 2 patients, respectively. Success rate of the technique was 98.4% (120/122). Major complication rate was 0.8% (1/120), and minor complication rate was 7.5% (9/120). Clinical indications: PEG, PED and PEJ were applied for long-term enteral nutritional support in 88 patients, gastrointestinal decompression in 25 patients, and transfusing external drainage bile to gastrointestinal tract in 5 patients. Two radiation enteritis patients used PEG for gastrointestinal decompression preoperatively and long-term enteral nutritional support postoperatively. CONCLUSION: PEG, PED PEJ and DPEJ are easily handled, effective and safe, and may be widely used in clinical practice.

Effects of endostatin on expression of vascular endothelial growth factor and its receptors and neovascularization in colonic carcinoma implanted in nude mice.

AIM: To investigate the antiangiogenic effects of endostatin on colonic carcinoma cell line implanted in nude mice and its mechanism. METHODS: Nude mice underwent subcutaneous injection with LS-174t colonic carcinoma cell line to generate carcinoma and were randomly separated into two groups. Mice received injection of vehicle or endostatin every day for two weeks. After the tumor was harvested, the tumor volumes were determined, and the expressions of CD34, VEGF and Flk-1 were examined by immunohistochemical method. RESULTS: Tumor volume was significantly inhibited in the endostatin group (84.17%) and tumor weight was significantly inhibited in the endostatin group (0.197+/-0.049) compared to the control group (1.198+/-0.105) (F = 22.56, P = 0.001), microvessel density (MVD) was significantly decreased in the treated group (31.857+/-3.515) compared to the control group (100.143+/-4.290) (F = 151.62, P<0.001). Furthermore, the expression of Flk-1 was significantly inhibited in the treated group (34.29%) compared to the control group (8.57%) (chi(2) = 13.745, P = 0.001). However no significant decrease was observed in the expression of vascular endothelial growth factor (VEGF) between these two groups (chi(2) = 0.119,P = 0.730). CONCLUSION: Endostatin can inhibit tumor growth and angiogenesis by blocking Vegf/Flk-1 pathway. This experiment provides the theory basis for developing a new anti-carcinoma drug through studying the properties of anti-angiogenesis inhibitors.