title: Overexpression of MAGE-D4 in colorectal cancer is a potentially prognostic biomarker and immunotherapy target.
abstract: Melanoma-associated antigen D4 (MAGE-D4) is a novel member of MAGE family. This study aimed to examine the expression and immunogenicity of MAGE-D4 in colorectal cancer (CRC) to determine its potential as a prognosis and immunotherapeutic target. The expression of MAGE-D4 mRNA and protein was determined by RT-PCR and immunohistochemistry (IHC) in CRCs with paired adjacent non-tumor tissues, colorectal adenomas and normal colorectal tissues, respectively. Sera from 64 CRC patients were tested for MAGE-D4 antibody by ELISA. MAGE-D4 mRNA was more frequently expressed in CRCs (76.7%, 46/60) than in adjacent non-tumor tissues (15.0%, 9/60). MAGE-D4 protein was detected in all the CRC tissues tested, 70.0% of which showed high expression. There was no MAGE-D4 protein detected in any paired adjacent non-tumor tissue. No MAGE-D4 expression was found in colorectal adenomas and normal colorectal tissues by either RT-PCR or immunohistochemistry. Patients with high MAGE-D4 protein expression had significantly shorter overall survival than those with low MAGE-D4 protein expression (median, 68.6 vs 122.2 months; P=0.030). Furthermore, multivariate analysis exhibited high MAGE-D4 protein expression had a trend toward an independent prognostic factor (hazard ratio: 6.124; P=0.050). Humoral immunity to MAGE-D4 was detected in 12 of 64 (18.8%) CRC patients' sera but not in 77 healthy donors. There was no correlation between MAGE-D4 expression, serum antibody and clinicopathological parameters. These findings suggest MAGE-D4 may serve as a potentially prognostic biomarker and an attractive target of immunotherapy in CRC.
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Qing-Mei
authors.initials: QM
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Shu-Jia
authors.initials: SJ
authors.lastname: He
authors.affiliation: Department of Oral and Maxillofacial Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Fan
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Guo-Rong
authors.initials: GR
authors.lastname: Luo
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Su-Fang
authors.initials: SF
authors.lastname: Zhou
authors.affiliation: Department of Surgery, First Affiliated Hospital, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Shao-Wen
authors.initials: SW
authors.lastname: Xiao
authors.affiliation: Department of Histology and Embryology, School of Pre-clinical Medicine, Guangxi Medical University Nanning 530021, Guangxi Zhuang Autonomous Region, China.
authors.forename: Xiao-Xun
authors.initials: XX
authors.lastname: Xie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology* / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; C120897:MAGED1 protein, human; D009363:Neoplasm Proteins
keywords: MAGE-D4; Melanoma-associated antigen; colorectal cancer; serum immunoreactivity