title: Macrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody-based therapy.
abstract: Macrophage inhibitory factor 1 (MIC1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC1 for esophageal squamous cell carcinoma (ESCC). Serum MIC1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC, CEA, CA199 and CA724, and the value as a prognostic indicator was also evaluated. The expression of MIC1 in ESCC cell lines, tissues were detected, and the inhibition of MIC1 antibody on ESCC was carried out in vitro and in vivo. The results showed that the serum MIC1 of ESCC was significantly higher than normal groups (P < 0.001), and was positively associated with tumor invasion (P = 0.030) as well as lymph node metastasis (P = 0.007). The sensitivity of MIC1 was significantly better than SCC, CEA, CA199 and CA724, especially for stage I ESCC. Patients with higher serum MIC1 also had a poorer prognosis in relapse-free (P = 0.050) and tumor-specific survival (P = 0.005). In vitro studies showed that the expression of MIC1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC1 in tumor tissues was significantly higher than paired adjacent normal tissues (P = 0.001). The antibody of MIC1 inhibited the tumor growth (P < 0.001), and showing preference for tumor tissues in xenograft model. The decreased formation of neovascularization lumen may be involved in the mechanism. We conclude that MIC1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC.
authors.affiliation: State Key Laboratory of Molecular Oncology, Department of Etiology and Carcinogenesis, Cancer Institute and Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Wang
authors.forename: Xing-Ran
authors.initials: XR
authors.lastname: Jiang
authors.forename: Xi-Ying
authors.initials: XY
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Shun
authors.initials: S
authors.lastname: He
authors.forename: Fei-Yue
authors.initials: FY
authors.lastname: Feng
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.forename: Shih-Hsin
authors.initials: SH
authors.lastname: Lu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000097:blood* / Q000276:immunology* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000097:blood / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D011379:Prognosis; D011897:Random Allocation; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: Diagnosis; esophageal squamous cell carcinoma; macrophage inhibitory factor 1; prognosis; target