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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 2/2009

01-02-2009 | Laboratory and Translational Research

Identification of Calreticulin as a Prognosis Marker and Angiogenic Regulator in Human Gastric Cancer

Authors: Chiung-Nien Chen, MD, PhD, Cheng-Chi Chang, PhD, Ting-En Su, Wen-Ming Hsu, MD, PhD, Yung-Ming Jeng, MD, Ming-Chih Ho, MD, PhD, Fon-Jou Hsieh, MD, Po-Huang Lee, MD, PhD, Min-Liang Kuo, PhD, Hsinyu Lee, PhD, King-Jen Chang, MD, PhD

Published in: Annals of Surgical Oncology | Issue 2/2009

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Abstract

The purpose of this study was to identify genes of interest for a subsequent functional and clinical cohort study using complementary (c)DNA microarrays. cDNA microarray hybridization was performed to identify differentially expressed genes between tumor and nontumor specimens in 30 gastric cancer patients. Subsequent functional studies of the selected gene were carried out, including cell cycle analysis, cell migration analysis, analyses of vascular endothelial growth factor (VEGF) and placenta growth factor (PlGF), and oligo-microarray studies using two pairs of stable cell lines of the selected gene. Another independent cohort study of 79 gastric cancer patients was conducted to evaluate the clinical significance of the selected gene in human gastric cancer. Calreticulin (CRT) was selected for further investigation. Two pairs of stable cell lines of CRT overexpression and CRT knockdown were constructed to perform functional studies. CRT enhanced gastric cancer cell proliferation and migration. Overexpressed CRT upregulated the expression and secretion of PlGF and VEGF. CRT had a reciprocal effect on connective tissue growth factor (CTGF) expression. Positive immunohistochemical staining of calreticulin was significantly correlated with high microvessel density (MVD) (p = 0.014), positive serosal invasion (p = 0.013), lymph node metastasis (p = 0.002), perineural invasion (p = 0.008), and poor patient survival (p = 0.0014). Multivariate survival analysis showed that CRT, MVD, and serosal invasion were independent prognosticators. We conclude that CRT overexpression enhances angiogenesis, and facilitates proliferation and migration of gastric cancer cells, which is in line with the association of CRT with MVD, tumor invasion, lymph node metastasis, and survival in gastric cancer patients.
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Metadata
Title
Identification of Calreticulin as a Prognosis Marker and Angiogenic Regulator in Human Gastric Cancer
Authors
Chiung-Nien Chen, MD, PhD
Cheng-Chi Chang, PhD
Ting-En Su
Wen-Ming Hsu, MD, PhD
Yung-Ming Jeng, MD
Ming-Chih Ho, MD, PhD
Fon-Jou Hsieh, MD
Po-Huang Lee, MD, PhD
Min-Liang Kuo, PhD
Hsinyu Lee, PhD
King-Jen Chang, MD, PhD
Publication date
01-02-2009
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 2/2009
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-008-0243-1

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