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Poor prognosis of hexokinase 2 overexpression in solid tumors of digestive system: a meta-analysis

Jiayuan Wu, Liren Hu, Fenping Wu, Lei Zou _ and Taiping He

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Oncotarget. 2017; 8:32332-32344. https://doi.org/10.18632/oncotarget.15974

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Abstract

Jiayuan Wu1,2,*, Liren Hu3,*, Fenping Wu4, Lei Zou5 and Taiping He6

1 Clinical Research Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China

2 Nutritional Department, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China

3 Department of Epidemiology and Health Statistics, School of Public Health, Guangdong Medical University, Zhanjiang, People’s Republic of China

4 Department of Radiotherapy, The Seventh People’s Hospital of Chengdu, The Oncology Hospital of Chengdu, Chengdu, People’s Republic of China

5 Department of Hepatobiliary Surgery, The First People’s Hospital of Yunnan Province, Kunming, People’s Republic of China

6 School of Public Health, Guangdong Medical University, Zhanjiang, People’s Republic of China

* These authors have contributed equally to this work

Correspondence to:

Lei Zou, email:

Jiayuan Wu, email:

Taiping He, email:

Keywords: hexokinase 2, solid tumors, digestive system, prognosis, meta-analysis

Received: October 24, 2016 Accepted: February 28, 2017 Published: March 07, 2017

Abstract

Several previous studies have reported the prognostic value of hexokinase 2 (HK2) in digestive system tumors. However, these studies were limited by the small sample sizes and the results were inconsistent among them. Therefore, we conducted a meta-analysis based on 15 studies with 1932 patients to assess the relationship between HK2 overexpression and overall survival (OS) of digestive system malignancies. The relationship of HK2 and clinicopathological features was also evaluated. Hazard ratio (HR) or odds ratio (OR) with its 95% confidence intervals (CI) were calculated to estimate the effect size. Positive HK2 expression showed poor OS in all tumor types (HR = 1.75 [1.41-2.18], P < 0.001). When stratified by tumor type, the impact of HK2 overexpression on poor prognosis was observed in gastric cancer (HR = 1.77 [1.25-2.50], P < 0.001), hepatocellular carcinoma (HR = 1.87 [1.58-2.21], P < 0.001), and colorectal cancer (HR = 2.89 [1.62-5.15], P < 0.001), but not in pancreatic ductal adencarcinoma (HR = 1.11 [0.58-2.11], P = 0.763). Furthermore, high HK2 expression was significantly associated with some phenotypes of tumor aggressiveness, such as large tumor size (OR = 2.03 [1.10-3.74], P = 0.024), positive lymph node metastasis (OR = 2.05 [1.39-3.02], P < 0.001), advanced clinical stage (OR = 2.17 [1.21-3.89], P = 0.009) and high alpha fetoprotein level (OR = 1.47 [1.09-2.02] P = 0.013). In summary, HK2 might act as a prognostic indicator and a potential therapeutic target of these digestive system cancers.


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