Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers

Xiaochen Wang, Xiyong Liu, Angela Ying Jian Li, Lirong Chen, Lily Lai, Her Helen Lin, Shuya Hu, Lifang Yao, Jiaping Peng, Sofia Loera, Lijun Xue, Bingsen Zhou, Lun Zhou, Shu Zheng, Peiguo Chu, Suzhan Zhang, David Kong Ann, Yun Yen

Research output: Contribution to journalArticle

107 Citations (Scopus)

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 γ-H2AX in HCT-116 and SW480 cells post γ-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.

Original languageEnglish
Pages (from-to)2570-2580
Number of pages11
JournalClinical Cancer Research
Volume17
Issue number8
DOIs
Publication statusPublished - Apr 15 2011
Externally publishedYes

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varespladib methyl
Colorectal Neoplasms
Neoplasm Metastasis
Survival
Biomarkers
HCT116 Cells
Adjuvant Radiotherapy
Kaplan-Meier Estimate
Survival Analysis
Proportional Hazards Models
Research Design
Radiotherapy
Multivariate Analysis
Survival Rate
Immunohistochemistry
Odds Ratio
Staining and Labeling
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers. / Wang, Xiaochen; Liu, Xiyong; Li, Angela Ying Jian; Chen, Lirong; Lai, Lily; Lin, Her Helen; Hu, Shuya; Yao, Lifang; Peng, Jiaping; Loera, Sofia; Xue, Lijun; Zhou, Bingsen; Zhou, Lun; Zheng, Shu; Chu, Peiguo; Zhang, Suzhan; Ann, David Kong; Yen, Yun.

In: Clinical Cancer Research, Vol. 17, No. 8, 15.04.2011, p. 2570-2580.

Research output: Contribution to journalArticle

Wang, X, Liu, X, Li, AYJ, Chen, L, Lai, L, Lin, HH, Hu, S, Yao, L, Peng, J, Loera, S, Xue, L, Zhou, B, Zhou, L, Zheng, S, Chu, P, Zhang, S, Ann, DK & Yen, Y 2011, 'Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers', Clinical Cancer Research, vol. 17, no. 8, pp. 2570-2580. https://doi.org/10.1158/1078-0432.CCR-10-2542
Wang, Xiaochen ; Liu, Xiyong ; Li, Angela Ying Jian ; Chen, Lirong ; Lai, Lily ; Lin, Her Helen ; Hu, Shuya ; Yao, Lifang ; Peng, Jiaping ; Loera, Sofia ; Xue, Lijun ; Zhou, Bingsen ; Zhou, Lun ; Zheng, Shu ; Chu, Peiguo ; Zhang, Suzhan ; Ann, David Kong ; Yen, Yun. / Overexpression of HMGA2 promotes metastasis and impacts survival of colorectal cancers. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 8. pp. 2570-2580.
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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 γ-H2AX in HCT-116 and SW480 cells post γ-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.",
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AU - Wang, Xiaochen

AU - Liu, Xiyong

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AU - Lin, Her Helen

AU - Hu, Shuya

AU - Yao, Lifang

AU - Peng, Jiaping

AU - Loera, Sofia

AU - Xue, Lijun

AU - Zhou, Bingsen

AU - Zhou, Lun

AU - Zheng, Shu

AU - Chu, Peiguo

AU - Zhang, Suzhan

AU - Ann, David Kong

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N2 - 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 γ-H2AX in HCT-116 and SW480 cells post γ-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.

AB - 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 γ-H2AX in HCT-116 and SW480 cells post γ-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.

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