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      The combination of novel immune checkpoints HHLA2 and ICOSLG: A new system to predict survival and immune features in esophageal squamous cell carcinoma


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          Studies on immune checkpoint inhibitors targeting B7-CD28 family pathways in esophageal squamous cell carcinoma (ESCC) have shown promising results. However, a comprehensive understanding of B7-CD28 family members in ESCC is still limited. This study aimed to construct a novel B7-CD28 family-based prognosis system to predict survival in patients with ESCC. We collected 179 cases from our previously published microarray data and 86 cases with qPCR data. Specifically, 119 microarray data (GSE53624) were used as a training set, whereas the remaining 60 microarray data (GSE53622), all 179 microarray data (GSE53625) and an independent cohort with 86 qPCR data were used for validation. The underlying mechanism and immune landscape of the system were also explored using bioinformatics and immunofluorescence. We examined 13 well-defined B7-CD28 family members and identified 2 genes (ICSOLG and HHLA2) with the greatest prognostic value. A system based on the combination HHLA2 and ICOSLG (B7-CD28 signature) was constructed to distinguish patients as high- or low-risk of an unfavorable outcome, which was further confirmed as an independent prognostic factor. As expected, the signature was well validated in the entire cohort and in the independent cohort, as well as in different clinical subgroups. The signature was found to be closely related to immune-specific biological processes and pathways. Additionally, high-risk group samples demonstrated high infiltration of Tregs and fibroblasts and distinctive immune checkpoint panels. Collectively, we built the first, practical B7-CD28 signature for ESCC that could independently identify high-risk patients. Such information may help inform immunotherapy-based treatment decisions for patients with ESCC.

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          With increasing incidence and mortality, cancer is the leading cause of death in China and is a major public health problem. Because of China's massive population (1.37 billion), previous national incidence and mortality estimates have been limited to small samples of the population using data from the 1990s or based on a specific year. With high-quality data from an additional number of population-based registries now available through the National Central Cancer Registry of China, the authors analyzed data from 72 local, population-based cancer registries (2009-2011), representing 6.5% of the population, to estimate the number of new cases and cancer deaths for 2015. Data from 22 registries were used for trend analyses (2000-2011). The results indicated that an estimated 4292,000 new cancer cases and 2814,000 cancer deaths would occur in China in 2015, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death. Residents of rural areas had significantly higher age-standardized (Segi population) incidence and mortality rates for all cancers combined than urban residents (213.6 per 100,000 vs 191.5 per 100,000 for incidence; 149.0 per 100,000 vs 109.5 per 100,000 for mortality, respectively). For all cancers combined, the incidence rates were stable during 2000 through 2011 for males (+0.2% per year; P = .1), whereas they increased significantly (+2.2% per year; P < .05) among females. In contrast, the mortality rates since 2006 have decreased significantly for both males (-1.4% per year; P < .05) and females (-1.1% per year; P < .05). Many of the estimated cancer cases and deaths can be prevented through reducing the prevalence of risk factors, while increasing the effectiveness of clinical care delivery, particularly for those living in rural areas and in disadvantaged populations.
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                Author and article information

                Genes Dis
                Genes Dis
                Genes & Diseases
                Chongqing Medical University
                21 August 2020
                March 2022
                21 August 2020
                : 9
                : 2
                : 415-428
                [a ]Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, PR China
                [b ]Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, PR China
                Author notes
                []Corresponding author. Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Beijing 100021, PR China. prof.jiehe@ 123456gmail.com

                These authors contributed equally to this work.

                © 2020 Chongqing Medical University. Production and hosting by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                : 23 March 2020
                : 23 June 2020
                : 14 August 2020
                Full Length Article

                esophageal cancer,hhla2,icoslg,immune checkpoint,immunotherapy


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