Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis

OncoTargets and Therapy, Mar 2018

Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis Gang Wang,1,* Qian Wang,1,* Zhengyan Li,2,* Chaoxu Liu,3 Xianli He1 1Department of General Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, China; 2Department of Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China; 3Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China *These authors contributed equally to this work Abstract: Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96–3.13) and OS (pooled HR =2.66, 95% CI: 2.04–3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78–3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer. Keywords: digestive system neoplasm, TPX2, meta-analysis, prognosis

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Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis

OncoTargets and Therapy Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis Gang w ang 2 Qian w ang 2 Zhengyan Li 1 Chaoxu Liu 0 Xianli He 2 0 Department of General Surgery, Huashan Hospital, Fudan University , Shanghai , China 1 Department of Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University , Xi'an , China 2 Department of General Surgery, Tangdu Hospital, Fourth Military Medical University , Xi'an , China Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays an important role in spindle assembly and dynamics. However, the clinical and prognostic value of TPX2 in the digestive system cancers remains unclear. The objective of this review was to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. The software Stata 12.0 was used to analyze the outcomes, including OS, disease-free survival (DFS), and clinicopathological characteristics. A total of 10 eligible studies with 906 patients were included. Elevated TPX2 expression was significantly associated with poor DFS (pooled hazard ratio [HR] =2.48, 95% confidence interval [CI]: 1.96-3.13) and OS (pooled HR =2.66, 95% CI: 2.04-3.48) of digestive system malignancies. Subgroup analyses showed that cancer type, sample size, study quality, and laboratory detection methods did not alter the significant prognostic value of TPX2. Additionally, TPX2 expression was found to be an independent predictive factor for DFS (HR =2.31, 95% CI: 1.78-3.01). TPX2 expression might be associated with TNM stage and pathological grade in digestive system cancer. In conclusion, TPX2 is an independent prognostic factor for survival of patients with digestive system cancer. Furthermore, its overexpression is associated with TNM stage and pathological grade in digestive system cancer. digestive system neoplasm; TPX2; meta-analysis; prognosis - open access to scientific and medical research *These authors contributed equally to this work Introduction Digestive system cancers, one of the most common malignancies, have overtaken cardiovascular disease and infectious diseases as a major cause of morbidity and mortality in the world.1–3 They cause approximately 2.9 million deaths per year.4 Although novel targeted therapies for terminal cancer patients are emerging, the application range is still limited.5 Therefore, it is of great importance to identify applicable prognostic biomarkers to improve the unfavorable prognosis. Xenopus kinesin-like protein 2 (TPX2), a 100 kDa protein, was first described by Heidebrecht et al in 1997.6 Human TPX2, a microtubule-associated protein located in chromosome 20q11.2,7,8 was reported to play an important role in spindle assembly and dynamics.9,10 In addition, TPX2 was found to participate in the regulation of cell mitosis or meiosis.11,12 Overexpression of TPX2 could cause DNA aneuploidy and polyploidy.13,14 The aberrant expression of TPX2 could inhibit normal mitosis and lead to carcinogenesis. Thus, TPX2 expression might have great potential for a more precise evaluation of progression of malignancy. Among numerous independent studies, the clinical predictive value of TPX2 in patients with cancer, especially digestive system cancer, remains controversial. A recently published work by Liu et al revealed a significant relationship of positive TPX2 to cancer stage III/IV and cancer grade of differentiation.15 Huang et al also showed that TPX2 level was positively associated with (TNM) tumor stage and Edmondson-Steiner grading.16 In obvious contrast, TPX2 expression was not correlated with TNM stage, cancer grade of differentiation, and tumor capsule according to the study by Liang et al.17 No correlation between TPX2 expression and tumor staging, grading, or TNM stage was indicated.18 The conflicting results lead to an unresolved issue on the relationship of TPX2 expression with clinical outcomes of cancer patients. Therefore, we performed the meta-analysis to evaluate the association of TPX2 expression with disease-free survival (DFS), overall survival (OS), and clinicopathological features of digestive system cancers. Selection criteria inclusion criteria ( 1 ) Cohort studies and case-control studies. ( 2 ) Studies investigating any type of digestive system cancers. ( 3 ) Studies providing data for the estimation of the hazard ratio (HR) for OS or DFS with 95% confidence intervals (CIs) included. ( 4 ) Studies where the association between TPX2 and clinical prognosis was clarified. ( 5 ) Studies of TPX2 overexpression based on primary cancer tissues. ( 6 ) The most samples and most informative studies when the duplicate studies were published. exclusion criteria ( 1 ) Studies irrelevant to digestive system cancers. 1230 ( 2 ) Studies which assessed pat (...truncated)


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Gang Wang, Qian Wang, Zhengyan Li, Chaoxu Liu, Xianli He. Clinical value of Xenopus kinesin-like protein 2 as a prognostic marker in patients with digestive system cancers: a systematic review and meta-analysis, OncoTargets and Therapy, 2018, pp. 1229-1243, DOI: 10.2147/OTT.S150829