title: Overexpression of colorectal cancer oncogene CHRDL2 predicts a poor prognosis.
abstract: Bone morphogenetic proteins (BMPs) both promote and suppress tumorigenesis, and multiple BMP antagonists reportedly contribute to cancer progression. In this study, we demonstrated that the BMP antagonist Chordin-like 2 (CHRDL2) is upregulated in colorectal cancer (CRC) tissues, and that CHRDL2 levels correlate with clinical features of CRC patients, including tumor size, TNM staging, and tumor differentiation. In addition, survival rate and Cox proportional hazards model analyses showed that high CHRDL2 levels correlate with a poor prognosis in CRC. Moreover, CHRDL2 promoted CRC cell proliferation in vitro and in vivo, perhaps through up-regulation of Cyclin D1 and down-regulation of P21. Co-immunoprecipitation assays showed that CHRDL2 bound to BMPs, which inhibited p-Smad1/5, thereby promoting CRC cell proliferation and inhibiting apoptosis. These results suggest CHRDL2 could serve as a biomarker of poor prognosis in CRC, and provide evidence that CHRDL2 acts as an oncogene in human CRC, making it a novel potential therapeutic target.
authors.affiliation: Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Ziyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Cancer Institute of Traditional Chinese Medicine & Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Sui
authors.affiliation: Interventional Cancer Institute of Integrative Medicine & Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
authors.forename: Zhongze
authors.initials: Z
authors.lastname: Fan
authors.affiliation: Department of Medical Oncology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D015513:Oncogene Proteins / Q000096:biosynthesis*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: C477338:CHRDL2 protein, human; D016326:Extracellular Matrix Proteins; D015513:Oncogene Proteins
keywords: BMP; CHRDL2; apoptosis; colorectal cancer; proliferation