Overexpression of HMGA2 Promotes Metastasis and Impacts Survival of Colorectal Cancers

• Published in: Clinical cancer research Vol. 17; no. 8; pp. 2570 - 2580
• Main Authors: XIAOCHENWANG, XIYONGLIU, LIJUN XUE, BINGSEN ZHOU, LUN ZHOU, SHU ZHENG, PEIGUO CHU, SUZHAN ZHANG, KONG ANN, David, YUN YEN, LI, Angelaying-Jian, CHEN, Lirong, LAI, Lily, LIN, Her Helen, SHUYA HU, LIFANG YAO, JIAPING PENG, LOERA, Sofia
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-04-2011
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - biosynthesis; Blotting, Western; Cell Line, Tumor; Colon - metabolism; Colon - pathology; Colon - radiation effects; Colorectal Neoplasms - metabolism; Colorectal Neoplasms - pathology; Female; Gastroenterology. Liver. Pancreas. Abdomen; HCT116 Cells; HEK293 Cells; Histones - metabolism; HMGA2 Protein - biosynthesis; HMGA2 Protein - genetics; Humans; Immunohistochemistry - statistics & numerical data; Kaplan-Meier Estimate; Logistic Models; Male; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Pharmacology. Drug treatments; Prognosis; Proportional Hazards Models; Retrospective Studies; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Colonic disease; Rectal disease; Colorectal cancer; Gene overexpression; Digestive diseases; Intestinal disease; Malignant tumor; Metastasis; Survival; Cancer
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-10-2542

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).
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.
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).
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.