Article

S100A4 over-expression underlies lymph node metastasis and poor prognosis in colorectal cancer.

Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
World Journal of Gastroenterology (Impact Factor: 2.43). 01/2011; 17(1):69-78. DOI: 10.3748/wjg.v17.i1.69
Source: PubMed

ABSTRACT To develop lymph node metastasis (LNM)-associated biomarkers for colorectal cancer (CRC) using quantitative proteome analysis.
Differences in protein expression between primary CRC with LNM (LNM CRC) and without LNM (non-LNM CRC) were assessed using methyl esterification stable isotope labeling coupled with 2D liquid chromatography followed by tandem mass spectrometry (2D-LC-MS/MS). The relationship to clinicopathological parameters and prognosis of candidate biomarkers was examined using an independent sample set.
Forty-three proteins were found to be differentially expressed by at least 2.5-fold in two types of CRC. S100A4 was significantly upregulated in LNM CRC compared with non-LNM CRC, which was confirmed by Western blotting, immunohistochemistry and real-time quantitative polymerase chain reaction. Further immunohistochemistry on another 112 CRC cases showed that overexpression of S100A4 frequently existed in LNM CRC compared with non-LNM CRC (P<0.001). Overexpression of S100A4 was significantly associated with LNM (P<0.001), advanced TNM stage (P<0.001), increased 5-year recurrence rate (P<0.001) and decreased 5-year overall survival rate (P<0.001). Univariate and multivariate analyses indicated that S100A4 expression was an independent prognostic factor for recurrence and survival of CRC patients (P<0.05).
S100A4 might serve as a powerful biomarker for LNM and a prognostic factor in CRC.

Download full-text

Full-text

Available from: Li Qi Xie, Nov 11, 2014
0 Followers
 · 
120 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: S100A4 protein, a member of the S100 superfamily of calcium-binding proteins, is frequently observed in various types of human cancers, including colorectal cancer (CRC). Our previous investigations have demonstrated that the overexpression of S100A4 is associated with lymph node metastasis and poor prognosis in CRC; however, its biological roles in CRC remain unclear. In the present study, we compared the expression of S100A4 at the mRNA and protein levels in six CRC cell lines, and found that the expression levels roughly coincided with their invasiveness. Using RNA interference, we suppressed S100A4 expression in SW620 CRC cells with highly invasive potential and S100A4 high expression. The specific knockdown of S100A4 strongly suppressed cell growth, migration and invasion activities. Furthermore, employing metastasis-related gene mRNA microarrays, we found four genes to be significantly dysregulated (more than 2-fold) after downregulation of S100A4, including three downregulated genes (MMP9, MMP10 and CDH11) and one upregulated gene (TIMP4). Our present results indicate that S100A4 may positively regulate tumor cell proliferation, invasion and metastasis associated with multiple molecules. Thus, the inhibition of S100A4 might be a potentially novel approach to treatment for CRC.
    Oncology Reports 12/2011; 27(4):917-22. DOI:10.3892/or.2011.1598 · 2.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical and experimental studies have suggested a link between S100 gene ex-pression and neoplastic disorders, however, the molecular mechanisms of this associa-tion are not well understood. The aim of this review was to conduct a comprehensive literature search in order to understand the possible underlying molecular mechanisms of this association. We also discuss their application as diagnostic and prognostic mark-ers in colorectal and hepatocellular carcinoma. EVIDENCE ACQUISITIONS: We searched Pubmed (NLM) and Web of Science (ISI Web of Knowledge). S100 genes display a complex expression pattern in colorectal and hepatocel- lular carcinoma. They are expressed in tumor and/or tumor stroma cells, and they exert both pro- and antitumorigenic actions. In view of this complexity, it becomes clear that S100 proteins might act as both friend and foe. The biological role of the S100 genes is predicted to depend on the relative contributions of the different cell types at specific stages of tumor progression. Further research is required in order to uncover the functional role of S100 genes in tumorigenesis. Answers to this issue are needed before we can more fully un-derstand the clinical relevance of S100 protein expression within epithelial tumors, with regard to their potential applicability as biomarkers for diagnosis and therapy decisions.
    Hepatitis Monthly 10/2012; 12(10 HCC):e7240. DOI:10.5812/hepatmon.7240 · 1.80 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Epithelial to mesenchymal transition (EMT) promotes tumor progression and invasion. As no study has focused on gastroesophageal junction (GEJ) tumors, the expression of three EMT-related proteins (S100A4, vimentin, and Snail1) was investigated with the aim of assessing their pathologic and prognostic significance. Resection specimens were obtained from 104 patients who underwent surgery for GEJ adenocarcinoma, without preoperative chemotherapy. Three tissue cores were obtained from each of the tumor body (TB), luminal surface (LS), and invasive edge (IE) to produce tissue microarrays, and immunohistochemical staining was performed. The microarrays were scored independently by two observers. The demographic and histopathologic details of the patients were collected. Overall positive expression was observed in 88 (S100A4, 85%), 16 (vimentin, 14%), and 92 (Snail1, 89%) tumors. Staining for S100 A4 was positive in 79 (76%) of TB, 69 (66%) of IE, and 69 (66%) of LS specimens. Staining for vimentin was positive in 7 (6%) of TB, 11 (11%) of IE, and 5 (5%) of LS specimens. Staining for Snail1 was positive in 83 (80%) of TB, 51 (49%) of IE, and 78 (75%) of LS specimens. Positive staining of TB for S100A4 (P = 0.04) and Snail1 at IE (P = 0.01) was associated with involvement of circumferential resection margins. Positive staining for S100A4 in the TB (P = 0.02) and LS (P = 0.01) was associated with poor 5-year overall survival. Vimentin had no statistically significant relationships with pathologic factors or outcome. The acquisition of mesenchymal protein S100A4 is associated with a poor prognosis in patients with GEJ tumors who undergo potentially curative surgery, and LS samples can be used to obtain prognostic information. Increased EMT-related protein expression (S100A4, Snail1) is associated with the involvement of circumferential resection margin.
    Diseases of the Esophagus 10/2012; 27(5). DOI:10.1111/j.1442-2050.2012.01435.x · 2.06 Impact Factor