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Int J Clin Exp Pathol 2013;6(11):2515-2522
High expression of inositol polyphosphate phosphatase-like 1 associates with
unfavorable survival in hepatocellular carcinoma
Maoying Fu, Xuefeng Gu, Huihui Ni, Wei Zhang, Feng Chang, Li Gong, Xiaoxiao Chen, Jiang Li, Liang Qiu, Chuanbing Shi, Jun Bao
Department of Infectious Diseases, The First People’s Hospital of Kunshan Affiliated with Jiangsu University, Suzhou 215000, China; The Key
Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of Health,
Nanjing Medical University, Nanjing 210029, China; Department of Pathology, Jiangsu Province Geriatric Institute, Nanjing 210029, China;
Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, China; Department of
Gastroenterology, Jiangsu Province Geriatric Institute, Nanjing 210029, China. Equal contributors.
Received September 2, 2013; Accepted September 29, 2013; Epub October 15, 2013; Published November 1, 2013
Abstract: Inositol polyphosphate phosphatase-like 1 (INPPL1), also known as SH2-containing inositol 5’-phosphatase 2 (SHIP2), has been
suggested to act downstream of the PI3K/AKT pathway and play an important function in tumor development and progression. However, the
associations between SHIP2 expression and the clinical features to determine its clinicopathologic significance in hepatocellular carcinoma
(HCC) have not been investigated. In the present study, one-step quantitative PCR reverse transcription-polymerase chain reaction (qPCR) and
immunohistochemistry (IHC) analysis with HCC tissue microarrays (TMA) were employed to evaluate the expression of SHIP2 in HCC. The
results showed that SHIP2 expression in the mRNA and protein levels was significantly higher in HCC tissue than in corresponding non-
cancerous tissue (p = 0.0014 and p < 0.001, respectively). The expression of SHIP2 protein in HCC was related to tumor differentiation, α-
fetoprotein level, liver cirrhosis, and five-year survival rate (all p < 0.05). Kaplan-Meier method and log-rank test indicated that high expression of
SHIP2 (p = 0.017) and tumor differentiation (p = 0.036) showed significant correlations with poor prognosis of HCC patients. The data indicate
that SHIP2 expression is correlated with significant characteristics of HCC, and it may be useful as an unfavorable prognostic factor in HCC.
Keywords: INPPL1, SHIP2, HCC, TMA, qPCR, immunohistochemistry
Address correspondence to: Dr. Chuanbing Shi, Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University,
Nanjing, China. Tel: +86-25-5850-9833; Fax: +86-25-5850-9994; E-mail: firstname.lastname@example.org; Dr. Jun Bao, Department of
Gastroenterology, Jiangsu Province Geriatric Institute, Nanjing, China. Tel: +86-25-8663-1726; Fax: +86-25-8663-1726; E-mail: njbaojun@163.