Open AccessMacrophage inhibitory factor 1 acts as a potential biomarker in patients with esophageal squamous cell carcinoma and is a target for antibody‐based therapy
Author(s) -
Wang XiaoBing,
Jiang XingRan,
Yu XiYing,
Wang Lin,
He Shun,
Feng FeiYue,
Guo LiPing,
Jiang Wei,
Lu ShihHsin
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12331
Subject(s) - antibody , cancer research , gdf15 , in vivo , carcinoma , cell culture , cell , metastasis , cancer , medicine , biology , immunology , pathology , biochemistry , genetics , microbiology and biotechnology
Macrophage inhibitory factor 1 ( MIC 1) is frequently altered in various cancers. The aim of this study was to investigate the clinical significance of MIC 1 for esophageal squamous cell carcinoma ( ESCC ). Serum MIC 1 of 286 ESCC and 250 healthy subjects was detected, the diagnostic performance was assessed and compared with SCC , CEA , CA 199 and CA 724, and the value as a prognostic indicator was also evaluated. The expression of MIC 1 in ESCC cell lines, tissues were detected, and the inhibition of MIC 1 antibody on ESCC was carried out in vitro and in vivo . The results showed that the serum MIC 1 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 MIC 1 was significantly better than SCC , CEA , CA 199 and CA 724, especially for stage I ESCC . Patients with higher serum MIC 1 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 MIC 1 was upregulated in 37.5% (3/8) ESCC cell lines and 45% (18/40) tissues, and the transcription of MIC 1 in tumor tissues was significantly higher than paired adjacent normal tissues ( P = 0.001). The antibody of MIC 1 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 MIC 1 plays an important role in the progression of ESCC and can serve as a potential biomarker and therapeutic target for ESCC .