PurposeTo develop a cerebrospinal fluid (CSF) miRNA diagnostic biomarker for glioblastoma.Experimental DesignGlioblastoma tissue and matched CSF from the same patient (obtained prior to tumor manipulation) were profiled by TaqMan OpenArray® Human MicroRNA Panel. CSF miRNA profiles from glioblastoma patients and controls were created from three discovery cohorts and confirmed in two validation cohorts.ResultsmiRNA profiles from clinical CSF correlated with those found in glioblastoma tissues. Comparison of CSF miRNA profiles between glioblastoma patients and non-brain tumor patients yielded a tumor “signature” consisting of nine miRNAs. The “signature” correlated with glioblastoma tumor volume (p=0.008). When prospectively applied to cisternal CSF, the sensitivity and specificity of the ‘signature’ for glioblastoma detection were 67% and 80%, respectively. For lumbar CSF, the sensitivity and specificity of the signature were 28% and 95%, respectively. Comparable results were obtained from analyses of CSF extracellular vesicles (EVs) and crude CSF.ConclusionWe report a CSF miRNA signature as a “liquid biopsy” diagnostic platform for glioblastoma.

BackgroundRecent studies indicated that some glycolytic enzymes are complicated, multifaceted proteins rather than simple components of the glycolytic pathway. FBP1 plays a vital role in glucose metabolism, but its role in gastric cancer tumorigenesis and metastasis has not been fully understood.MethodsThe prognostic value of FBP1 was first studied in The Cancer Genome Atlas (TCGA) database and validated in in-house database. The effect of FBP1 on cell proliferation and metastasis was examined in vitro. Nonparametric test and Log-rank test were used to evaluate the clinical significance of FBP1 expression.ResultsIn the TCGA cohort, FBP1 mRNA level were shown to be predictive of overall survival in gastric cancer (P = 0.029). In the validation cohort, FBP1 expression were inversely correlated with advanced N stage (P = 0.021) and lymphovascular invasion (P = 0.011). Multivariate Cox regression analysis demonstrated that FBP1 was an independent predictor for both overall survival (P = 0.004) and disease free survival (P<0.001). Functional studies demonstrated that ectopic FBP1 expression inhibited proliferation and invasion in gastric cancer cells, while silencing FBP1 expression had opposite effects (P<0.05). Mechanically, FBP1 serves as a tumor suppressor by inhibiting epithelial-mesenchymal transition (EMT).ConclusionsDownregulation of FBP1 promotes gastric cancer metastasis by facilitating EMT and acts as a potential prognostic factor and therapeutic target in gastric cancer.

The leading cause of death among cancer patients is tumor metastasis. Tumor-derived exosomes are emerging as mediators of metastasis. In the present study, we demonstrated that exosomes play a pivotal role in the metastatic progression of colorectal cancer. First, a nude mouse model of colorectal cancer liver metastasis was established and characterized. Then, we demonstrated that exosomes from a highly liver metastatic colorectal cancer cell line (HT-29) could significantly increase the metastatic tumor burden and distribution in the mouse liver of Caco-2 colorectal cancer cells, which ordinarily exhibit poor liver metastatic potential. We further investigated the mechanisms by which HT-29-derived-exosomes influence the liver metastasis of colorectal cancer and found that mice treated with HT-29-derived exosomes had a relatively higher level of CXCR4 in the metastatic microenvironment, indicating that exosomes may promote colorectal cancer metastasis by recruiting CXCR4-expressing stromal cells to develop a permissive metastatic microenvironment. Finally, the migration of Caco-2 cells was significantly increased following treatment with HT-29-derived exosomes in vitro, further supporting a role for exosomes in modulating colorectal tumor-derived liver metastasis. The data from the present study may facilitate further translational medicine research into the prevention and treatment of colorectal cancer liver metastasis.