Elevated serum DAND5 is associated with metastasis and predicts poor prognosis in colorectal cancer.

BACKGROUND: The biologic and clinical significance of DAND5 remains unknown in colorectal cancer (CRC). OBJECTIVE: Herein, we investigated the function of DAND5 and evaluated its clinical significance in both serum and matched primary tumors in patients with CRC. METHODS: The role of DAND5 was explored in CRC cells and clinical significance of DAND5 was investigated in CRC patients (n = 217) and healthy controls (n = 63). RESULTS: Knockdown of DAND5 significantly decreased CRC cell proliferation, migration and invasion partly associated with epithelial-mesenchymal transition phenotype. Serum DAND5 levels in CRC were significantly higher than in normal controls and accurately distinguished CRC from healthy subjects. High serum DAND5 levels were significantly correlated with tumor differentiation, large tumor size, advanced Tumor Node Metastasis (TNM) stage, lymph node and liver metastasis, high carcinoembryonic antigen level, recurrence, poor overall and disease-free survival. Serum DAND5 level, together with lymph node metastasis, were independent prognostic factors for CRC patients. High DAND5 protein expression in CRC tissues was increased according to TNM stage. A significant positive correlation existed between serum DAND5 levels and matched DAND5 expression in CRC tissues. CONCLUSION: Our data provide novel evidence for the clinical significance of DAND5 as a potential biomarker for CRC prognosis.

Identification of ß-glucosidase 1 as a biomarker and its high expression in hepatocellular carcinoma is associated with resistance to chemotherapy drugs.

CONTEXT AND OBJECTIVE: Long-term prognosis of hepatocellular carcinoma (HCC) patients is challenging, and novel biomarkers are needed to predict patient risk and serve as potential therapeutic target. RESULTS: We found ß-glucosidase 1 is significantly overexpressed and activated in primary HCC tissue and multiple HCC cell lines. ß-Glucosidase 1 expression is associated with predicting prognosis of HCC patients under chemotherapy. Silencing ß-glucosidase 1 inhibits growth and survival of HCC cells, with preferential inhibitory effects on high ß-glucosidase 1-expressing cells. Combination of chemo drug with ß-glucosidase 1 inhibitor sensitized HCC cells to chemotherapy. CONCLUSION: Our data support ß-glucosidase 1 as a HCC biomarker due to its prognosis significance.

MicroRNA-425-5p regulates chemoresistance in colorectal cancer cells via regulation of Programmed Cell Death 10.

Acquired chemoresistance represents a major obstacle in cancer treatment, the underlying mechanism of which is complex and not well understood. MiR-425-5p has been reported to be implicated tumorigenesis in a few cancer types. However, its role in regulating chemoresistance has not been investigated in colorectal cancer (CRC) cells. Microarray analysis was performed in isogenic chemosensitive and chemoresistant HCT116 cell lines to identify differentially expressed miRNAs. miRNA quantitative real-time PCR was used to detect miR-425-5p expression levels between drug resistant and parental cancer cells. MiR-425-5p mimic and inhibitor were transfected, followed by CellTiter-Glo(®) assay to examine drug sensitivity in these two cell lines. Western Blot and luciferase assay were performed to investigate the direct target of miR-425-5p. Xenograft mouse models were used to examine in vivo function of miR-425-5p. Our data showed that expression of miR-425-5p was significantly up-regulated in HCT116-R compared with parental HCT116 cells. Inhibition of miR-425-5p reversed chemoresistance in HCT116-R cells. Programmed cell death 10 (PDCD10) is the direct target of miR-425-5p which is required for the regulatory role of miR-425-5p in chemoresistance. MiR-425-5p inhibitor sensitized HCT116-R xenografts to chemo drugs in vivo. Our study demonstrated that miR-425-5p regulates chemoresistance of CRC cells by modulating PDCD10 expression level both in vitro and in vivo. MiR-425-5p may represent a new therapeutic target for the intervention of CRC.

Simultaneous Detection of α-Fetoprotein and Carcinoembryonic Antigen Based on Si Nanowire Field-Effect Transistors.

Primary hepatic carcinoma (PHC) is one of the most common malignancies worldwide, resulting in death within six to 20 months. The survival rate can be improved by effective treatments when diagnosed at an early stage. The α-fetoprotein (AFP) and carcinoembryonic antigen (CEA) have been identified as markers that are expressed at higher levels in PHC patients. In this study, we employed silicon nanowire field-effect transistors (SiNW-FETs) with polydimethylsiloxane (PDMS) microfluidic channels to simultaneously detect AFP and CEA in desalted human serum. Dual-channel PDMS was first utilized for the selective modification of AFP and CEA antibodies on SiNWs, while single-channel PDMS offers faster and more sensitive detection of AFP and CEA in serum. During the SiNW modification process, 0.1% BSA was utilized to minimize nonspecific protein binding from serum. The linear dynamic ranges for the AFP and CEA detection were measured to be 500 fg/mL to 50 ng/mL and 50 fg/mL to 10 ng/mL, respectively. Our work demonstrates the promising potential of fabricated SiNW-FETs as a direct detection kit for multiple tumor markers in serum; therefore, it provides a chance for early stage diagnose and, hence, more effective treatments for PHC patients.