1. The Department of Thoracic Surgery (Ⅲ), Shanxi Cancer Hospital, Taiyuan, Shanxi 030013, P.R. China.
2. Department of Pathology & Shanxi Key Laboratory of Carcinogenesis and Translational Research of Esophageal Cancer, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
3. Department of Pathology, The First Hospital, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
4. Department of Otorhinolaryngology, Shanxi Provincial People's Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi 030012, P.R. China.
5. Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, Shandong 250000, P.R. China.
#These authors contributed equally to this work.
Non-muscle myosin heavy chain 9 (MYH9) is one novel low frequency mutated gene identified in esophageal squamous cell carcinoma (ESCC) using next-generation sequencing. However, its clinical relevance, potential function and mechanisms remain elusive.
Methods: Genomic sequencing datas from 104 esophageal squamous cell carcinoma (ESCC) cases were screened a series of low frequency mutant genes. MYH9 was selected to further analyze its clinical significance, function and PCR-array was performed to explore its potential mechanism.
Results: MHY9 is a low frequency mutant gene with a mutation frequency of 2.88% in ESCC. Immunohistochemical analysis showed that MYH9 expression was significantly higher in ESCC tumor tissues, and the expression levels were associated with lymph node metastasis of ESCC patients. Moreover, we found that MYH9 knock-down led to inhibition of cell migration and invasion. PCR-array showed MYH9 knockdown led to a significant change of genes expression associated with angiogenesis and epithelial-to-mesenchymal transition (EMT). This observation is further confirmed in TCGA database of LUSC (lung squamous cell carcinoma), CESC (cervical squamous cell carcinomas) and HNSC (head and neck squamous cell carcinoma).
Conclusions: Collectively, our study identifies a novel role and mechanism of MYH9, highlights a significance of MYH9 as a metastatic biomarker, and offers potential therapeutic targets for ESCC patients harboring MYH9 mutations.
Keywords: MYH9, ESCC, angiogenesis, EMT