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Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers.


ABSTRACT: PURPOSE:This study aims to address the hypothesis that the high-mobility group A2 (HMGA2), an oncofetal protein, relates to survivability and serves as a prognostic biomarker for colorectal cancer (CRC). EXPERIMENTAL DESIGN:This is a retroprospective multiple center study. The HMGA2 expression level was determined by performing immunohistochemistry on surgical tissue samples of 89 CRCs from a training set and 191 CRCs from a validation set. The Kaplan-Meier analysis and COX proportional hazard model were employed to analyze the survivability. RESULTS:Multivariate logistic analysis indicated that the expression of HMGA2 significantly correlates with distant metastasis in training set (odds ratio, OR = 3.53, 95% CI: 1.37-9.70) and validation set (OR = 6.38, 95% CI: 1.47-43.95). Survival analysis revealed that the overexpression of HMGA2 is significantly associated with poor survival of CRC patients (P < 0.05). The adjusted HRs for overall survival were 2.38 (95% CI: 1.30-4.34) and 2.14 (95% CI: 1.21-3.79) in training and validation sets, respectively. Further investigation revealed that HMGA2 delays the clearance of ?-H2AX in HCT-116 and SW480 cells post ?-irradiation, which supports our finding that CRC patients with HMAG2-positive staining in primary tumors had augmented the efficacy of adjuvant radiotherapy (HR = 0.18, 95% CI: 0.04-0.63). CONCLUSION:Overexpression of HMGA2 is associated with metastasis and unequivocally occurred in parallel with reduced survival rates of patients with CRC. Therefore, HMGA2 may potentially serve as a biomarker for predicting aggressive CRC with poor survivability and as an indicator for better response of radiotherapy.

SUBMITTER: Wang X 

PROVIDER: S-EPMC3079060 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers.

Wang Xiaochen X   Liu Xiyong X   Li Angela Ying-Jian AY   Chen Lirong L   Lai Lily L   Lin Her Helen HH   Hu Shuya S   Yao Lifang L   Peng Jiaping J   Loera Sofia S   Xue Lijun L   Zhou Bingsen B   Zhou Lun L   Zheng Shu S   Chu Peiguo P   Zhang Suzhan S   Ann David Kong DK   Yen Yun Y  

Clinical cancer research : an official journal of the American Association for Cancer Research 20110120 8


<h4>Purpose</h4>This study aims to address the hypothesis that the high-mobility group A2 (HMGA2), an oncofetal protein, relates to survivability and serves as a prognostic biomarker for colorectal cancer (CRC).<h4>Experimental design</h4>This is a retroprospective multiple center study. The HMGA2 expression level was determined by performing immunohistochemistry on surgical tissue samples of 89 CRCs from a training set and 191 CRCs from a validation set. The Kaplan-Meier analysis and COX propor  ...[more]

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