Overexpression of HOXA13 as a Potential Marker for Diagnosis and Poor Prognosis of Hepatocellular Carcinoma

Overexpression of HOXA13 as a Potential Marker for Diagnosis and Poor Prognosis of Hepatocellular Carcinoma

TING-TING PAN,¹ WEI-DONG JIA,^2,3 QI-YANG YAO,² QI-KAI SUN,² WEI-HUA REN,² MEI HUANG,² JIE MA,² JIAN-SHENG LI,³ JIN-LIANG MA,³ JI-HAI YU,³ YONG-SHENG GE,³ WEN-BIN LIU,³ CHUAN-HAI ZHANG³ and GE-LIANG XU^2,3

¹Graduate school, Tianjin Medical University, Tianjin, P.R. China
²Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui Province, P.R. China
³Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui Province, P.R. China

HOXA13 is a member of homeobox genes that encode transcription factors regulating embryonic development and cell fate. Abnormal HOXA13 expression was reported in hepatocellular carcinoma (HCC), but its correlation with tumor angiogenesis and prognosis still remain unclear. This study was aimed to uncover the expression, diagnostic and prognostic significance of HOXA13 in HCC. Immunohistochemistry was performed to detect HOXA13 expression in HCC and corresponding paracarcinomatous tissues from 90 patients. Enzyme-linked immunosorbent assay was used to detect serum HOXA13 in 90 HCC patients and 20 healthy volunteers. Receiver operating characteristics was analyzed to calculate diagnostic accuracy of serum HOXA13, alpha-fetoprotein (AFP) and their combination. Immunoreactivity of HOXA13 was detected in 72.2% of HCC, and 12.2% of adjacent non-cancerous samples. HOXA13 expression was significantly associated with tumor size, microvascular invasion, pathological grade, tumor capsula status, AFP level, tumor-node-metastasis stage and positively correlated with VEGF (p < 0.001) and microvessel density (p < 0.001). The combination of serum HOXA13 and AFP had a markedly higher area under the curve than HOXA13 alone. HOXA13 expression was associated with unfavorable overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p < 0.001). Multivariate analysis indicated that patients with HOXA13-expressing tumors had a significantly shorter OS (p = 0.030) and DFS (p = 0.005) than those with HOXA13-negative tumors. Thus, HOXA13 expression possibly plays an important role in tumor angiogenesis, progression and prognosis of HCC. Moreover, we demonstrate that serum HOXA13 may serve as a biomarker for early HCC diagnosing and predicting outcome.

keywords —— Keywords: hepatocellular carcinoma; homeobox gene; HOXA13; prognosis; tumor angiogenesis

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Tohoku J. Exp. Med., 2014, 234, 209-219

Correspondence: Ge-Liang Xu, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, and Department of Hepatic Surgery, Affiliated Provincial Hospital of Anhui Medical University, NO. 17, Lujiang Road, Hefei, Anhui Province 230001, P.R. China.

e-mail: xugeliang2013@163.com