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Aim  Esophageal squamous cell carcinoma (ESCC) is a refractory digestive organ cancer that requires better treatment strategies. We have recently reported that the antidiabetic drug metformin exerts antitumor effects on ESCC by inhibition of nuclear factor kappa B (NF‐κB) nuclear translocation. In the present study, we focused on caspase recruitment domain family member 9 (CARD9), an essential signal adapter in NF‐κB activation to examine whether it can be used as a prognostic factor in ESCC.    Methods  We investigated CARD9 expression immunohistochemically in clinical samples obtained from 93 patients with ESCC who underwent curative esophagectomy. CARD9 expression was analyzed for correlation with clinicopathological characteristics and ESCC prognosis. The molecular effects were investigated by knocking down ESCC cells. Comprehensive RNA expression changes in these ESCC cells were detected by next‐generation sequencing (NGS).    Results  High CARD9 expression is significantly correlated with advanced tumor depth ( P  < .001), positive lymph node metastasis ( P  = .005) and advanced stage ( P  = .001). Kaplan‐Meier method and the log‐rank test showed that overall survival (OS) and disease‐free survival (DFS) were significantly poor in the high CARD9 expression group (OS:  P  = .027, DFS:  P  = .005). Univariate and multivariate analysis showed that high CARD9 expression is a significant poor prognostic factor for DFS. Cell proliferation and migration were suppressed by  CARD9  knockdown. NGS detected altered the expression of some RNAs including maternally expressed 3 ( MEG3 ).    Conclusion  High CARD9 expression is significantly associated with poor prognosis. Therefore, CARD9 expression may be a prospective prognostic biomarker in ESCC.

Caspase recruitment domain family member 9 expression is a promising biomarker in esophageal squamous cell carcinoma