To search for potential protein markers of colorectal cancer (CRC), the changes in protein expression levels between microdissected tumor cells and normal mucosa epithelia were analyzed by an acetylation stable isotopic labeling method coupled with linear quadrupole ion trap fourier transform mass spectrometry (LTQ-FTMS). In total, 137 proteins were up-regulated or down-regulated significantly in cancer by at least two-fold. Based on gene ontology analysis, the largest part of differential proteins were unknown for both subcellular localization and biological process. In particular, the significant up-regulation of transgelin-2 (TAGLN2) in CRC was validated by Western blot analysis and further evaluated by immunohistochemistry in paired tumor and normal mucosa samples from 120 consecutive CRC patients, 20 adenomas, and eight synchronous hepatic metastases of CRC. TAGLN2 expression was frequently observed in cancer cells, precancerous lesions, and hepatic metastases, whereas in normal epithelia expression was rarely observed. The overexpression of TAGLN2 was associated with lymph node and distant metastasis, advanced clinical stage (P < 0.001), and shorter overall survival in CRCs. Cox regression analysis indicated that high tumor-TAGLN2 expression represents an independent prognostic factor. Consequently, over-expression of TAGLN2 may serve as a new biomarker for predicting progression and prognosis of CRC. (Cancer Sci 2010; 101: 523-529) C olorectal cancer (CRC) is one of the most frequent malignancies and is listed as the third leading cause of cancer-related deaths worldwide. Treatments for CRC have made significant progress in recent years. However, most patients are diagnosed after the invasive cancer appears, which therefore restricts further attempts to improve the survival rate.(1) Consequently, the search for candidate biomarkers for early detection and prognostication of CRC is urgently required to guide early treatment and improve the prognosis of patients.As an overall and high-throughout protein analysis strategy, proteomics provides opportunities for the discovery of new biomarkers for the diagnosis of diseases.(2) In recent years, proteomic technology has been applied in the analysis of CRC (3)(4)(5) and has identified a number of differentially expressed proteins. However, very few of these results have been confirmed in the clinical setting and none of the identified potential marker proteins have been widely used for diagnosis or treatment of CRC in the clinic. Gel-based approaches such as two-dimensional electrophoresis (2-DE) and two-dimensional differential in-gel electrophoresis (2D-DIGE) are conventionally used for comparative proteomics in the field of cancer research. However, there are a number of technical difficulties associated with 2-DE protein separation that limits its applicability only to abundant and soluble proteins.(6) Recently, there has been increasing interest in applying mass spectrometry (MS)-based quantitative methods to proteomic efforts. Such approaches complement ...

MAPKs, particularly ERK subclass are overexpressed in the majority of gastric cancers. Overexpression of ERKs is correlated to TNM staging, serosa invasion, and lymph node involvement. The overexpression of p38 most likely plays a prominent role in certain morphological subtypes of gastric cancers. MEK-1 is also overexpressed in gastric cancer, particularly in metastatic lymph nodes. Upregulation of MAPK signal transduction pathways may play an important role in tumorigenesis and metastatic potential of gastric cancer.

Abstract. Gastric cancer (GC) is the one of the most common types of cancer in Asia. To better understand the molecular mechanisms underlying GC, and to seek new markers of tumor progression, we used a proteomics strategy to analyze the protein expression patterns in matched pairs of GC tissue and normal gastric mucosa of 8 GC patients. Comparative proteomic analysis, using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization timeof-flight mass spectrometry (MALDI-TOF-MS), revealed that 32 protein spots showed a >2-fold difference in intensity between tumor and normal tissues. Twenty-six proteins were up-regulated and 6 proteins were down-regulated in tumor tissue compared to control. Western blot analysis confirmed differential expression for 9 proteins, including AGR2, ENO1, GDI2, GRP78, GRP94, PPIA, PRDX1, PTEN and VDAC1. Immunohistochemical staining of a tissue microarray, derived from 145 GC patients, with antibodies for each of the 9 proteins demonstrated a significant association between the level of protein immunostaining and the clinical features of the disease in the donor. The identified proteins were functionally classified using bioinformatics methods, showing that the 9 proteins identified were related to BCL2, BAX, ERBB2 and CASP3 proteins and involved in the process of apoptosis. These proteomic data provide potentially valuable insights into both the biology of GC and the identity of biomarkers for tumor progression. We propose ENO1, GRP78, GRP94, PPIA, PRDX1 and PTEN as potential GC biomarkers.

Sarcandra glabra | Molecular networks | Natural products | Structural elucidation | Peroxides Sarcaglarols AD (1-4), two pairs of lindenane−monoterpene heterodimers fused by a 1,2-dioxane moiety, were discovered and isolated from the leaves of Sarcandra glabra guided by MS/MS molecular networking-based strategy. Their planar structures, absolute configurations of basic skeleton and flexible polyhydric side chain were established by analysis of HRESIMS, NMR spectroscopic data, ECD spectrum, and the X-ray diffraction study of isopropylidene derivatives. An intermolecular [2+2+2] cycloaddition may play a key role in the biosynthesis pathway of the 1,2-dioxane moiety fused lindenane−monoterpene heterodimer skeleton, which can be recognized as the biogenetic precursors of our previous reported lindenane−normonoterpene conjugates. In addition, compounds 1, 3 and 4 exhibited moderate inhibitory effects of lipid accumulation in free fatty acid-exposed L02 cells.

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