Danlei Song1,2, Yongjian Wei3, Yuping Hu1,4, Yueting Sun1,2, Min Liu2, Qian Ren2, Zenan Hu2, Qinghong Guo2, Yuping Wang2, Yongning Zhou5,6. 1. The First Clinical Medical College, Lanzhou University, Lanzhou, China. 2. Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China. 3. The First Department of Hepatobiliary and Pancreatic Surgery, Cangzhou Central Hospital, Cangzhou, China. 4. Hospital of Reproductive Medicine, The First Hospital of Lanzhou University, Lanzhou, China. 5. The First Clinical Medical College, Lanzhou University, Lanzhou, China. zhouyn@lzu.edu.cn. 6. Department of Gastroenterology, Key Laboratory for Gastrointestinal Diseases of Gansu Province, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu Province, China. zhouyn@lzu.edu.cn.
Abstract
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high heterogeneity. Research on molecular mechanisms involved in the process of tumor origination and progression is extremely limited to investigating mechanisms of molecular typing for ESCC. METHODS: After comprehensively analyzing the gene expression profiles in The Cancer Genome Atlas and Gene Expression Omnibus databases, we identified four immunotypes of ESCC (referred to as C1-C4) based on the gene sets of 28 immune cell subpopulations. The discrepancies in prognostic value, clinical features, drug sensitivity, and tumor components between the immunotypes were individually analyzed. RESULTS: The ranking of immune infiltration is C1 > C4 > C3 > C2. These subtypes are characterized by high and low expression of immune checkpoint proteins, enrichment and insufficiency of immune-related pathways, and differential distribution of immune cell subgroups. Poorer survival was observed in the C1 subtype, which we hypothesized could be caused by an immunosuppressive cell population. Fortunately, C1's susceptibility to anti-PD-1 therapy offers hope for patients with poor prognosis in advanced stages. On the other hand, C4 is sensitive to docetaxel, which may offer novel treatment strategies for ESCC in the future. It is worth noting that immunophenotyping is tightly bound to the abundance of stromal components and stem cells, which could explain the tumor immune escape to some extent. Ultimately, determination of hub genes based on the C1 subtypes provides a reference for the discovery of immunotarget drugs against ESCC. CONCLUSION: The identification of immunophenotypes in our study provides new therapeutic strategies for patients with ESCC.
PURPOSE: Esophageal squamous cell carcinoma (ESCC) is a malignant tumor with high heterogeneity. Research on molecular mechanisms involved in the process of tumor origination and progression is extremely limited to investigating mechanisms of molecular typing for ESCC. METHODS: After comprehensively analyzing the gene expression profiles in The Cancer Genome Atlas and Gene Expression Omnibus databases, we identified four immunotypes of ESCC (referred to as C1-C4) based on the gene sets of 28 immune cell subpopulations. The discrepancies in prognostic value, clinical features, drug sensitivity, and tumor components between the immunotypes were individually analyzed. RESULTS: The ranking of immune infiltration is C1 > C4 > C3 > C2. These subtypes are characterized by high and low expression of immune checkpoint proteins, enrichment and insufficiency of immune-related pathways, and differential distribution of immune cell subgroups. Poorer survival was observed in the C1 subtype, which we hypothesized could be caused by an immunosuppressive cell population. Fortunately, C1's susceptibility to anti-PD-1 therapy offers hope for patients with poor prognosis in advanced stages. On the other hand, C4 is sensitive to docetaxel, which may offer novel treatment strategies for ESCC in the future. It is worth noting that immunophenotyping is tightly bound to the abundance of stromal components and stem cells, which could explain the tumor immune escape to some extent. Ultimately, determination of hub genes based on the C1 subtypes provides a reference for the discovery of immunotarget drugs against ESCC. CONCLUSION: The identification of immunophenotypes in our study provides new therapeutic strategies for patients with ESCC.
Authors: Zachary Wilmer Reichenbach; Mary Grace Murray; Reshu Saxena; Daniel Farkas; Erika G Karassik; Alena Klochkova; Kishan Patel; Caitlin Tice; Timothy M Hall; Julie Gang; Henry P Parkman; Sarah J Ward; Marie-Pier Tétreault; Kelly A Whelan Journal: Adv Cancer Res Date: 2019-06-10 Impact factor: 6.242