title: Melanoma differentiation-associated gene-7/interleukin-24 as a potential prognostic biomarker and second primary malignancy indicator in head and neck squamous cell carcinoma patients.
abstract: The significance of melanoma differentiation-associated gene-7/interleukin-24 (MDA-7/IL-24) expression in head and neck squamous cell carcinoma (HNSCC) remains unclear. This study was designed to investigate and evaluate the clinical significance of MDA-7/IL-24 expression in HNSCC by detecting expression by immunostaining in 131 HNSCC specimens. The function of MDA-7/IL-24 was investigated by real-time polymerase chain reaction (PCR) and Western blot in Ad5.mda-7-infected HNSCC cell lines. Our results showed that MDA-7/IL-24 was mainly expressed in the cytoplasm of HNSCC cells. MDA-7/IL-24 high patients presented with a favorable postoperative prognosis compared with MDA-7/IL-24 low patients, and high expression of MDA-7/IL-24 was significantly correlated with a lower incidence of second primary malignancies (SPMs) in the head and neck regions. In vitro assays showed that high expression of MDA-7/IL-24 could upregulate the expression of the epithelial terminal differentiation markers cytokeratin (KRT) 1, KRT4, KRT13, phosphorylated endoplasmic reticulum stress protein (p)-EIF2a, and the apoptosis-related protein cleaved caspase-3. It also downregulated the epithelial proliferative markers KRT5, KRT14, Integrin β4, and anti-apoptosis protein Bcl-2, which might be partially involved in the underlying mechanisms of Ad.mda-7-mediated HNSCC differentiation and apoptosis. Our results indicate that MDA-7/IL-24 can be a prognostic biomarker and an indicator of second primary malignancies (SPM) in HNSCC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, 22 Zhongguancun Avenue South, Haidian, Beijing, 100081, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Zhien
authors.initials: Z
authors.lastname: Feng
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Wu
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.forename: Yinfei
authors.initials: Y
authors.lastname: Pu
authors.forename: Huan
authors.initials: H
authors.lastname: Bian
authors.forename: Yixiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Chuanbin
authors.initials: C
authors.lastname: Guo
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000150:complications* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D000099180:Interleukin-24
chemical_list: D014408:Biomarkers, Tumor; D007378:Interleukins; D012333:RNA, Messenger; D000099180:Interleukin-24
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