Gastrointestinal cancer is the most prevalent cancer among malignant tumors,with a upward trend in incidence.Since there is absence of specific clinical manifestation as well as low diagnostic rate,patients diagnosed with cancer of digestive tract are mostly in intermediate or advanced stages.Therefore,they lose the best chance of surgery and have a poor prognosis. Metabonomics,a kind of high sensitivity research technology,shows great potential in the exploration of occurrence and development of malignant tumor.The aim of this study was to review the progress of application in gastrointestinal cancer by metabonomics.

Objective To evaluate the value of urinary normal and modified nucleosides in the diagnosis of primary gallbladder carcinoma.Methods Between March 2011 to September 2012,28 patients with primary carcinoma of the gallbladder (PCG) were included in this study.Spontaneous urine samples were collected and 10 kinds of urinary nucleosides in the sample were determined by reversed-phase high performance liquid chromatography method.Another 62 patients with benign gallbladder disease and 70 healthy volunteers were enrolled as controls.Routine clinical tumor markers,including serum CA19-9 and CA125 levels of the PCG patients were also evaluated.Results 10 kinds of nucleoside had a good linear correlation (r＞0.99),and the recovery rate was between 87.4％ ～121.5％ range,and the accuracy rate was between 87.7％ ～121.3％,and the RSD of precision was between 1.5％～10.5％ range.In addition to adenosine and cytidine,the mean levels of the rest of the urinary nucleosides in the PCG group were much higher than those of the controls (P＜0.01).Based on principal component analysis,89.3％ of the PCG patients were correctly identified,which was much higher than those detected by CA19-9 (60.7％) and CA125 (67.9％) (P＜0.01).Conclusion Urinary nucleosides may become additional tumor markers which when combined with other clinical methods may help in the screening and early diagnosis of primary gallbladder cancer.

Previous studies suggest that the reduction of SMAD3 (mothers against decapentaplegic homolog 3) has a great impact on tumor development, but its exact pathological function remains unclear. In this study, we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues, in which LAMP2A (lysosome-associated membrane protein type 2A) was significantly up-regulated. LAMP2A is a key rate-limiting protein of chaperone-mediated autophagy (CMA), a lysosome pathway of protein degradation that is activated in glioma. We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ, which has been proposed to be a targeting sequence for CMA. In vitro, we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition, which was regulated by LAMP2A and interacted with HSC70 (heat shock cognate 71 kDa protein). Using isolated lysosomes, amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process, which affected the CMA pathway in which SMAD3 was involved. Similarly, down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion. Taken together, these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3. Therefore, targeting the SMAD3-LAMP2A-mediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.