Identification of transgelin‐2 as a biomarker of colorectal cancer by laser capture microdissection and quantitative proteome analysis

Abstract

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 ...

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