• Yue Yu, Zhihua Li, Chenjun Huang, Haisheng Fang, Fei Zhao, Yue Zhou, Xianglong Pan, Qifan Li, Yu Zhuang, Liang Chen, Jing Xu, and Wei Wang.
• Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
• Cancer Med. 2020 Jan 1; 9 (2): 575-585.

BackgroundThe poor outcome of patients with esophageal squamous cell carcinoma (ESCC) highlights the importance of the identification of novel effective prognostic biomarkers. We aimed to identify a clinically applicable prognostic immunohistochemistry (IHC) panel for ESCC.MethodsAn integrated analysis was performed to screen and establish a prognostic panel using exome sequencing profile from 81 pairs of ESCC samples and RNA expression microarray data from 119 ESCC subjects. Two independent ESCC cohorts were recruited as training and validation groups to test the prognostic value.ResultsThree genes were selected, namely, ANO1, GAL, and MMP3, which were aberrantly expressed in ESCC tumor tissues (P < .001). Among them, ANO1 and MMP3 were reserved for the construction of the prognostic panel due to their significant association with the prognosis of ESCC patients (P = .015 and P < .001). Patients with both ANO1+ and MMP3+ had a poorer prognosis than that with ANO1-/MMP3+, ANO1+/MMP3-, or ANO1-/MMP3 - in both the training set and validation set (P < .001). Receiver operating characteristic analysis showed that the combination of IHC panel and eighth American Joint Commission on Cancer staging yielded a better prognostic predictive efficacy compared with the two indexes alone (P < .001, area under curve: 0.752). Finally, a nomogram was created by integrating the IHC markers and clinicopathological risk factors to predict prognosis with a C-index of 0.695 (95% confidence interval: 0.657-0.734).ConclusionUsing an integrated multistage screening strategy, we identified and validated a valuable prognostic IHC panel for ESCC.© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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