Background:We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear.Methods:We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT–PCR.Results:CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-β signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients.Conclusion:PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.

The TRC method seems to be a useful alternative to the CellSearch system for clinically detecting CTCs in patients with metastatic CRC.

Perioperative administration of sivelestat improves postoperative respiratory function in patients after esophagectomy.

Background: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of the global DNA methylation level. In some types of human neoplasms, the LINE-1 methylation level is attracting interest as a useful marker for predicting cancer prognosis. However, the prognostic significance of LINE-1 hypomethylaiton in gastric cancer remains unclear. Methods: Using 96 resected gastric cancer specimens, we quantified the LINE-1 methylation using bisulfite-pyrosequencing technology. A Cox proportional hazards model was used to calculate the hazard ratio (HR), adjusted for tumor stage. Results: Gastric cancers showed significantly lower LINE-1 methylation levels compared to matched normal gastric mucosa (p<0.0001; N=50). The distribution of the LINE-1 methylation level in the 96 cancers was as follows: mean, 71.0; median, 72.9; SD, 12.2; range, 28.0-97.5; interquartile range, 66.7-77.7 (all in 0-100 scale). LINE-1 methylation level was not associated with tumor stage, T status, or N status (all P>0.05). In univariate analysis, LINE-1 hypermethylation tumor (more than 77.7) tended to have longer overall survival (log-rank p=0.10; univariate HR=0.50, 95% CI 0.19-1.12, p=0.097), although that was not statistically significant. However, in stage-adjusted analysis, LINE-1 hypermethylation was significantly associated with overall survival (HR=0.38, 95% CI 0.14-0.87, p=0.021). Conclusions: LINE-1 hypermethylation in gastric cancer is associated with longer survival, suggesting that it has potential for use as a prognostic biomarker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4101. doi:1538-7445.AM2012-4101