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Background. Analysis of aberrant hypermethylation in stool DNA might provide a novel strategy for noninvasive detection of colorectal cancer. Aims. To explore the feasibility of detecting hypermethylation in Spastic paraplegia-20 promoter as a stool-based DNA marker for detection of colorectal cancer. Methods. We collected 96 tissue and stool samples from patients with colorectal cancer and 30 stool samples healthy individuals. Results. Hypermethylated Spastic paraplegia-20 occurs in 85.4% (82/96) of patients with colorectal cancer in the tissue samples. In the stool samples, the results indicate 80.2% (77/96) sensitivity and 100% (30/30) specificity of the test for detecting colorectal cancer by using the stool samples as a noninvasive method. Conclusions. The study reveals that hypermethylation in Spastic paraplegia-20 promoter is a highly specific and sensitive biomarker for screening colorectal cancer in stool samples as a noninvasive method.

Rapidly proliferating cancer cells rely on increased glucose consumption for survival. The glucose analog 2-deoxy-D-glucose (2DG) cannot complete glycolysis and inhibits the growth of many types of cancers. It is unknown whether reduced glycolysis inhibits the growth of pancreatic cancer. Activation of nerve growth factor (NGF)-neurotrophic tyrosine kinase receptor type 1 (NTRK1) signaling leads to enhanced proliferation of these cells. We investigated the effect of 2DG treatment on the viability of NTRK1-transfected pancreatic cancer cells. After treatment with 2DG, the viability of pancreatic cancer cells was evaluated by MTT assay. SB203580 (a specific inhibitor of the p38-MAPK pathway) and PD98059 (an MAP2K1 [mitogen-activated protein kinase kinase 1, previously, MEK1] inhibitor) were used to inhibit p38-MAPK and ERKs, respectively. The percentage of apoptotic cells was determined by flow cytometry. Overexpression of NTRK1 in pancreatic cancer cells resulted in increased cell proliferation, which was reduced by PD98059-mediated inhibition of ERKs but not by suppression of p38-MAPK with SB203580. After treatment with 2DG, the percentage of apoptotic cells was greater in those with high expression of NTRK1 than in cells with low NTRK1 expression. Blocking the p38-MAPK pathway with SB203580 effectively abolished the apoptosis induced by 2DG. We conclude that pancreatic cancer cells with a high expression of NTRK1 are more sensitive to 2DG-induced apoptosis, through the p38-MAPK pathway.

Homeobox genes are known to be critically important in tumor development and progression. The BP1 (Beta Protein 1) gene, an isoform of DLX4, belongs to the Distal-less (DLX) subfamily of homeobox genes and encodes a homeodomain-containing transcription factor. Our studies have shown that the BP1 gene was overexpressed in 81% of primary breast cancer and its expression was closely correlated with the progression of breast cancer. However, the exact role of BP1 in breast has yet to be elucidated. Therefore, it is important to explore the potential transcriptional targets of BP1 via whole genome-scale screening. In this study, we used the chromatin immunoprecipitation on chip (ChIP-on-chip) and gene expression microarray assays to identify candidate target genes and gene networks, which are directly regulated by BP1 in ER negative (ER-) breast cancer cells. After rigorous bioinformatic and statistical analysis for both ChIP-on-chip and expression microarray gene lists, 18 overlapping genes were noted and verified. Those potential target genes are involved in a variety of tumorigenic pathways, which sheds light on the functional mechanisms of BP1 in breast cancer development and progression.