Decreased expression of insulin-like growth factor binding protein 6 is associated with gastric adenocarcinoma prognosis

Zeng,Changqing; Feng,Xingyu; Wang,Wei; Lv,Lin; Fang,Cheng; Chi,Liangjie; Huang,Liangxiang; Zhou,Zhiwei

doi:10.3892/ol.2017.5993

Decreased expression of insulin-like growth factor binding protein 6 is associated with gastric adenocarcinoma prognosis

Authors:
- Changqing Zeng
- Xingyu Feng
- Wei Wang
- Lin Lv
- Cheng Fang
- Liangjie Chi
- Liangxiang Huang
- Zhiwei Zhou
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Affiliations: Department of Gastric Surgery, Sun Yat‑sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong 510060, P.R. China, Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong 510060, P.R. China, Department of Oncology, Guangzhou First People's Hospital, Guangzhou, Guangdong 510180, P.R. China, Department of Gastrointestinal Surgery, Fujian Provincial Hospital, Provincial Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China
Published online on: April 5, 2017 https://doi.org/10.3892/ol.2017.5993
Pages: 4161-4168
Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the expression and prognostic significance of insulin‑like growth factor binding protein 6 (IGFBP-6) in gastric adenocarcinoma. The expression of IGFBP‑6 was examined in 263 specimens from gastric adenocarcinoma patients using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blotting and immunohistochemical (IHC) staining. The association between IGFBP‑6 expression, clinicopathological factors and clinical outcomes was investigated. Akaike information criterion (AIC) and Harrell’s concordance index (c‑index) were used to evaluate the accuracy of the predictive prognosis. RT‑qPCR and western blotting results showed that IGFBP‑6 mRNA expression was lower in the tumors compared with that in adjacent non‑tumor tissues. IGFBP‑6 showed significantly decreased expression in 170 out of 263 patients based on IHC data and this was associated with a larger tumor size (P<0.001) and poorly‑differentiated adenocarcinoma (P=0.001), as well as with palliative gastrectomy (P=0.015). Additionally, decreased expression of IGFBP‑6 was associated with stage T3/4a/4b disease and lymph node‑positive metastasis (P<0.001). The association between decreased expression and a poor prognosis was revealed by Kaplan‑Meier curves. Cox regression model identified IGFBP‑6 as an independent prognostic factor. The prognostic value of the model with IGFBP‑6 expression (AIC, 924.881; c‑index, 0.878) was superior to that without IGFBP‑6 expression (AIC, 947.164; c‑index, 0.825). In conclusion, IGFBP‑6 involves the development and progression of gastric adenocarcinoma, and its decreased expression predicts poor clinical outcomes.

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