Association of MARCH7 with tumor progression and T-cell infiltration in esophageal cancer

MARCH7 与食管癌肿瘤进展和 T 细胞浸润的关系

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作者:Shivam Singh #, Arjumand Bano #, Anoop Saraya, Prasenjit Das, Rinu Sharma

Abstract

MARCH7 is an E3 ubiquitin ligase known to regulate neuronal development,T-cell proliferation, and cell and tissue differentiation. But, the altered expression of MARCH7 has been observed in various malignancies. Herein, the cellular localization and role of MARCH7 have been elucidated in esophageal squamous cell carcinoma (ESCC), the information regarding which is currently limited. To check the expression of MARCH7 and its correlation with immune cells infiltration in ESCC, immunohistochemical analysis was performed. RNAi approach was used to investigate the role of MARCH7 in esophageal cancer cells. Interestingly, we found a significantly higher expression of MARCH7 protein in 84% of ESCC tissues than in distant matched non-malignant tissues (p ≤ 0.001). In addition to this, immunohistochemistry results have shown a negative correlation between MARCH7 protein expression and tumor-infiltrating immune cells such as CD8 + T cells (r = - 0.633, p = 0.001) and PD1 + T cells (r = - 0.560, p = 0.005). Furthermore, MARCH7 silencing inhibited the ESCC cell growth and reduced the clonogenic and invasion/migration potential of ESCC cells. MARCH7 silencing also significantly increased E-cadherin protein levels in ESCC cells relative to those in negative control cells (p < 0.05). Thus, MARCH7 is oncogenic and might have a possible role in esophageal carcinogenesis. Moreover, E-cadherin may be a downstream target of MARCH7 in ESCC.

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