Prognostic value of pigment epithelium-derived factor for neoadjuvant radiation therapy in patients with locally advanced rectal carcinoma

  • Authors:
    • Haizhao Yi
    • Dengbo Ji
    • Tiancheng Zhan
    • Yunfeng Yao
    • Ming Li
    • Jinying Jia
    • Zhaowei Li
    • Jin Gu
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  • Published online on: July 12, 2016     https://doi.org/10.3892/ijo.2016.3620
  • Pages: 1415-1426
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Abstract

The aim of the study was to investigate the prognostic value of pigment epithelium-derived factor (PEDF) in locally advanced rectal carcinoma (LARC) treated with neoadjuvant radiation therapy (nRT). The level of PEDF expressing was examined in LARC tissues treated with nRT by immunohistochemistry and the prognostic significance of PEDF was analysed by univariate and multivariate survival analyses. We forced expression of PEDF in highly metastatic LoVo cells. The clonogenic survival assay was used to test the cellular sensitivity to radiation. Wound healing and Boyden chamber assays were used to detect cell migration and invasion. To assess the contribution of PEDF in vivo, we established tumor xenografts. The mechanisms of PEDF on cancer cells was analysed by bioinformatics. Our immunohistochemical staining of tissue samples revealed that prolonged DFS (77.1 vs 49.0%) and OS (87.1 vs 56.3%) was observed in PEDF-positive cases (P<0.001) following nRT. PEDF could be an independent factor for DFS [P=0.001; HR, 0.422 (95% CI, 0.249-0.717)] and OS [P=0.003; HR, 0.418 (95% CI, 0.234-0.749)]. Positive-expression of PEDF was negatively correlated with tumor differentiation (P<0.016), ypT stage (P<0.037), ypTNM stage (P<0.033), and ypN stage (P=0.006). Overexpression of PEDF in high metastatic cells enhanced radiosensitivity and, suppressed migration and invasion in vitro. In tumor xenografts, PEDF significantly suppressed tumor growth. Furthermore, by bioinformatics analysis, we found PEDF performs functions via activating P53 to regulate double-strand break repair pathway and activate the G protein activation pathway. Our findings indicate that PEDF was identified as a predictive candidate for nRT responsiveness. These findings may be used to stratify LARC patients and make alternative strategies for adjuvant treatment.
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October-2016
Volume 49 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yi H, Ji D, Zhan T, Yao Y, Li M, Jia J, Li Z and Gu J: Prognostic value of pigment epithelium-derived factor for neoadjuvant radiation therapy in patients with locally advanced rectal carcinoma. Int J Oncol 49: 1415-1426, 2016.
APA
Yi, H., Ji, D., Zhan, T., Yao, Y., Li, M., Jia, J. ... Gu, J. (2016). Prognostic value of pigment epithelium-derived factor for neoadjuvant radiation therapy in patients with locally advanced rectal carcinoma. International Journal of Oncology, 49, 1415-1426. https://doi.org/10.3892/ijo.2016.3620
MLA
Yi, H., Ji, D., Zhan, T., Yao, Y., Li, M., Jia, J., Li, Z., Gu, J."Prognostic value of pigment epithelium-derived factor for neoadjuvant radiation therapy in patients with locally advanced rectal carcinoma". International Journal of Oncology 49.4 (2016): 1415-1426.
Chicago
Yi, H., Ji, D., Zhan, T., Yao, Y., Li, M., Jia, J., Li, Z., Gu, J."Prognostic value of pigment epithelium-derived factor for neoadjuvant radiation therapy in patients with locally advanced rectal carcinoma". International Journal of Oncology 49, no. 4 (2016): 1415-1426. https://doi.org/10.3892/ijo.2016.3620