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Is insulin-like growth factor binding protein 2 associated with metastasis in lung cancer?

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Abstract

Insulin-like growth factor binding protein 2 (IGFBP2) is involved in the progression of many epithelial cancers. However, its role in non-small cell lung cancer (NSCLC), another type of epithelial cancer, remains unclear. We detected IGFBP2 expression using immunohistochemistry in surgically resected tumors from 110 NSCLC patients, 37 of which had metastases. The positive rate of IGFBP2 expression was compared between the metastatic and the non-metastatic group, and correlations of IGFBP2 expression with metastasis and overall survival were analyzed. We also investigated the expression of IGFBP2 in microvesicles (MVs) collected from primary lung cancer cell cultures, and in different locations of newly resected NSCLC tumors, using immunoblotting. The overall positive rate of IGFBP2 expression in lung cancer was 51.8 % and it was significantly higher in the metastatic group than in the non-metastatic group (70.3 and 42.5 % respectively, p < 0.01). And the higher the lymph node stage, the higher the positive rate. Cytoplasmic expression was predominant in the majority of the tumors. Based on multivariate regression analysis, IGFBP2 was correlated with metastasis and poor overall survival (Hazard ratio: 3.56 and 3.23 respectively). IGFBP2 was detectable in the MVs collected from IGFBP2 positive cell lines, and its expression was most abundant in the marginal region of the newly resected tumors. IGFBP2 is associated with metastasis and poor survival of lung cancer. Its presence in MVs and high abundance in the marginal region of tumors suggest that its association with metastasis may be related to tumor microenviroment remodeling in NSCLC.

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Abbreviations

IGFBP2:

Insulin-like growth factor binding protein 2

IGF:

Insulin-like growth factor

MVs:

Microvesicles

NSCLC:

Non-small cell lung cancer

TMA:

Tissue microarray

IRS:

The immunoreactive score

VEGF:

Vascular endothelial growth factor

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Acknowledgments

Acknowledgements of research support: This work was supported by the National Natural Science Foundation of China [81172226].

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No conflict of interest to be declared.

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Authors and Affiliations

  1. Department of Cardiothoracic Surgery, Xiangya Hospital, Central-South University, Changsha, 410078, Hunan, China

    Qinghua Hu, Lingjin Huang, Heng Zhang, Guoqiang Ling & Xuliang Chen

  2. Xiangya Medical School, Central-South University, Changsha, 410008, Hunan, China

    Xuyuan Kuang & Kejiang Li

  3. Department of Pathology, Xiangya Hospital, Central-South University, Changsha, 410078, Hunan, China

    Zhenghao Deng & Jianhua Zhou

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  1. Qinghua Hu
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  2. Lingjin Huang
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  3. Xuyuan Kuang
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  4. Heng Zhang
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  5. Guoqiang Ling
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  6. Xuliang Chen
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  7. Kejiang Li
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  8. Zhenghao Deng
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  9. Jianhua Zhou
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Correspondence to Lingjin Huang.

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Hu, Q., Huang, L., Kuang, X. et al. Is insulin-like growth factor binding protein 2 associated with metastasis in lung cancer?. Clin Exp Metastasis 31, 535–541 (2014). https://doi.org/10.1007/s10585-014-9647-4

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  • DOI: https://doi.org/10.1007/s10585-014-9647-4

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