Brief Article
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World J Gastroenterol. Jul 21, 2013; 19(27): 4309-4315
Published online Jul 21, 2013. doi: 10.3748/wjg.v19.i27.4309
Krüppel-like factor 8 overexpression is correlated with angiogenesis and poor prognosis in gastric cancer
Wen-Fei Wang, Juan Li, Lu-Tao Du, Li-Li Wang, Yong-Mei Yang, Yi-Min Liu, Hui Liu, Xin Zhang, Zhao-Gang Dong, Gui-Xi Zheng, Chuan-Xin Wang
Wen-Fei Wang, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leics, LE12 5RD, United Kingdom
Juan Li, Lu-Tao Du, Li-Li Wang, Yong-Mei Yang, Yi-Min Liu, Hui Liu, Xin Zhang, Zhao-Gang Dong, Gui-Xi Zheng, Chuan-Xin Wang, Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, Shandong Province, China
Author contributions: Wang WF and Li J contributed equally to this work; Wang WF, Li J and Wang CX designed the study and wrote the manuscript; Du LT and Yang YM summarized the immunostaining results which had been obtained by two non-author pathologists; Wang LL and Liu YM performed the research and analyzed the data; Liu H and Zhang X assisted in patient recruitment to the study and performed most of the lab work; Dong ZG and Zheng GX assisted in the patient interviews.
Supported by The Shandong Province Natural Science Foundation of China, No. ZR2010HZ004; and the National Key Clinical Medical Specialties Foundation
Correspondence to: Chuan-Xin Wang, Professor, Department of Clinical Laboratory, Qilu Hospital, Shandong University, 107 Wenhua Xi Road, Jinan 250012, Shandong Province, China. cxwang@sdu.edu.cn
Telephone: +86-531-82166801 Fax: +86-531-86927544
Received: March 3, 2013
Revised: May 17, 2013
Accepted: June 19, 2013
Published online: July 21, 2013
Processing time: 139 Days and 8.8 Hours
Abstract

AIM: To investigate Krüppel-like factor 8 (KLF8) expression in gastric cancer and its relationship with angiogenesis and prognosis of gastric cancer.

METHODS: One hundred and fifty-four patients with gastric cancer who underwent successful curative resection were retrospectively enrolled in the study. Fifty tumor-adjacent healthy gastric tissues (≥ 5 cm from the tumor margin) obtained during the original resection were randomly selected for comparative analysis. In situ expression of KLF8 and CD34 proteins were examined by immunohistochemistry. The intratumoral microvessel density (MVD) was determined by manually counting the immunostained CD34-positive endothelial cells in three consecutive high-magnification fields (× 200). The relationship between differential KLF8 expression and MVD was assessed using Spearman’s correlation coefficient test. χ2 test was performed to evaluate the effects of differential KLF8 expression on clinicopathologic factors. Kaplan-Meier and multivariate Cox survival analyses were used to assess the prognostic value of differential KLF8 expression in gastric cancer.

RESULTS: Significantly higher levels of KLF8 protein were detected in gastric cancer tissues than in the adjacent non-cancerous tissues (54.5% vs 34.0%, P < 0.05). KLF8 expression was associated with tumor size (P < 0.001), local invasion (P = 0.005), regional lymph node metastasis (P = 0.029), distant metastasis (P = 0.023), and tumor node metastasis (TNM) stage (P = 0.002), as well as the MVD (r = 0.392, P < 0.001). Patients with KLF8 positive expression had poorer overall survival (P < 0.001) and cancer-specific survival (P < 0.001) than those with negative expression. Multivariate analysis demonstrated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients (P = 0.035 and 0.042, respectively).

CONCLUSION: KLF8 is closely associated with gastric tumor progression, angiogenesis and poor prognosis, suggesting it may represent a novel prognostic biomarker and therapeutic target for gastric cancer.

Keywords: Gastric cancer; Krüppel-like factor 8; Angiogenesis; Prognosis

Core tip: In this study, we found that the expression of Krüppel-like factor 8 (KLF8) was up-regulated in resected gastric cancer tissues. The differential KLF8 expression was significantly associated with enhanced malignant potential, including tumor size, local invasion, regional lymph node metastasis, distant metastasis, and tumor node metastasis stage, as well as the intratumoral microvessel density. Multivariate analysis indicated that KLF8 expression independently affected both overall and cancer-specific survival of gastric cancer patients. Collectively, our findings suggest that KLF8 may be a predictive marker of clinical outcome and represent a novel target for anti-angiogenic therapy of gastric cancer patients.