title: Prognostic value of pigment epithelium-derived factor for neoadjuvant radiation therapy in patients with locally advanced rectal carcinoma.
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.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Haizhao
authors.initials: H
authors.lastname: Yi
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Dengbo
authors.initials: D
authors.lastname: Ji
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Tiancheng
authors.initials: T
authors.lastname: Zhan
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Jia
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Zhaowei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Gastrointestinal Surgery Ⅲ, Peking University Cancer Hospital and Institute, Haidian, Beijing 100142, P.R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D002465:Cell Movement; D018572:Disease-Free Survival; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D008297:Male; D051379:Mice; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism*; D011379:Prognosis; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy*; D015843:Serpins / Q000235:genetics* / Q000378:metabolism*; D016019:Survival Analysis; D016896:Treatment Outcome; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor