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

Abstract

e14116 Background: The high mobility group A2 (HMGA2) protein regulates the expression of a cohort of genes by either enhancing or suppressing their transcription. The change of HMGA2 mRNA or protein levels has been reported to correlate with malignant tumor phenotypes. Therefore, we hypothesized that the expression level of HMGA2 is related to cancer survival and serves as prognostic biomarkers for clinical outcome of colorectal cancers (CRCs). Methods: 191 consecutive CRCs who received surgical treatment in second affiliated hospital of Zhejiang University from 1999 to 2004 were entered into this outcome study. In addition, 89 CRCs from City of Hope were collected as validation set. Patients were periodically followed up for survival. The IHC study was conducted on tissue arrays to determine the expression of HMGA2 proteins. The Kaplan-Meier analysis and COX proportional hazard model were employed to conduct uni- and multi- variant survival analysis. Results: The IHC results displayed that the expression of HMGA2 could be seen significant higher in malignant tumor section in comparing corresponding normal colon epithelial cells. Univariate and multivariate logistic analysis indicated that the nuclear expression of HMGA2 is significantly related to distant metastasis among 191 CRCs (p < 0.05). Survival analysis revealed that the higher nuclear staining of HMGA2 is significantly related to poor survival of CRCs (p < 0.05). The adjusted hazard proportional ratios (HRs) are 1.81 (95% CI 1.04-3.12) and 1.86 (95% CI 1.08-3.22) for overall and progress-free survival respectively. Further analysis indicated that HMAG2 impacts the survival on CRCs at III-IV stage, rather than I-II stage. The HRs of HMGA2 at stage III-IV is 1.92 (95% CI 1.02-3.58) for overall survival, and 2.03 (95% CI 1.07-3.80) for progress-free survival. It was validated on stage III-IV CRCs from City of Hope (HRs=1.80 for overall survival, HRs=2.05 for progress-free survival). Conclusions: HMGA2 might play a critical role in promoting the invasion and metastasis phenotype of colorectal cancer. Overexpression of HMGA2 significantly impacts the survival on advanced CRCs. Therefore, HMGA2 may serve as a potential prognostic marker for predicting outcome of CRCs.