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      CD155 Overexpression Correlates With Poor Prognosis in Primary Small Cell Carcinoma of the Esophagus

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          Abstract

          CD155/TIGIT overexpression has been detected in various human malignancies; however, its expression status in primary small cell carcinoma of the esophagus (PSCCE) and its prognostic significance remain unclear. In this study, we aimed to explore the expression and prognostic value of CD155 and TIGIT in PSCCE. We detected CD155 and TIGIT expression in 114 cases of PSCCE using immunohistochemistry (IHC) and evaluated their relationship with the clinicopathological characteristics and survival of the patients. Survival analyses were performed using the Kaplan-Meier method and Cox proportional hazards model. Nomogram performance was assessed via the concordance index (C-index) and calibration plots. Decision curve analysis (DCA) was performed to evaluate the net benefit of the nomogram. We found that CD155 and TIGIT were overexpressed in PSCCE tissues, CD155 expression correlated positively with TIGIT ( p < 0.001) and was significantly associated with tumor size, T stage, distant metastasis, TNM stage, and Ki-67 score. TIGIT expression was also significantly associated with T stage, distant metastasis, and TNM stage. Patients with high CD155 and TIGIT expression had a significantly shorter overall survival (OS) and progression-free survival (PFS), while the multivariate model showed that CD155 expression and the therapeutic strategy are independent prognostic factors for PSCCE. In the validation step, OS was shown to be well-calibrated (C-index = 0.724), and a satisfactory clinical utility was proven by DCA. In conclusion, our findings revealed that CD155 and TIGIT are highly expressed in patients with PSCCE and are associated with shorter OS and PFS, supporting their role as prognostic biomarker.

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          Cancer statistics in China, 2015.

          Wanqing Chen, Rongshou Zheng, Peter D Baade … (2016)
          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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            First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer

            Leora Horn, Aaron Mansfield, Aleksandra Szczęsna … (2018)
            Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy.
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              TOX is a critical regulator of tumour-specific T cell differentiation

              Andrew C Scott, Friederike Dündar, Paul Zumbo … (2019)
              Tumour-specific CD8 T cell dysfunction is a differentiation state that is distinct from the functional effector or memory T cell states 1–6 . Here we identify the nuclear factor TOX as a crucial regulator of the differentiation of tumour-specific T (TST) cells. We show that TOX is highly expressed in dysfunctional TST cells from tumours and in exhausted T cells during chronic viral infection. Expression of TOX is driven by chronic T cell receptor stimulation and NFAT activation. Ectopic expression of TOX in effector T cells in vitro induced a transcriptional program associated with T cell exhaustion. Conversely, deletion of Tox in TST cells in tumours abrogated the exhaustion program: Tox-deleted TST cells did not upregulate genes for inhibitory receptors (such as Pdcd1, Entpd1, Havcr2, Cd244 and Tigit), the chromatin of which remained largely inaccessible, and retained high expression of transcription factors such as TCF-1. Despite their normal, ‘non-exhausted’ immunophenotype, Tox-deleted TST cells remained dysfunctional, which suggests that the regulation of expression of inhibitory receptors is uncoupled from the loss of effector function. Notably, although Tox-deleted CD8 T cells differentiated normally to effector and memory states in response to acute infection, Tox-deleted TST cells failed to persist in tumours. We hypothesize that the TOX-induced exhaustion program serves to prevent the overstimulation of T cells and activation-induced cell death in settings of chronic antigen stimulation such as cancer.
              Article 0 comments Cited 414 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Mol Biosci
                Journal ID (iso-abbrev): Front Mol Biosci
                Journal ID (publisher-id): Front. Mol. Biosci.
                Title: Frontiers in Molecular Biosciences
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 2296-889X
                Publication date (Electronic): 07 January 2021
                Publication date Collection: 2020
                Volume: 7
                Electronic Location Identifier: 608404
                Affiliations
                [1] 1Department of Radiation Oncology, The First Affiliated Hospital of China Medical University , Shenyang, China
                [2] 2Department of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical University , Yantai, China
                [3] 3Cheeloo College of Medicine, Shandong University , Jinan, China
                [4] 4Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, China
                [5] 5Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University , Jinan, China
                [6] 6Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences , Jinan, China
                [7] 7Department of Radiation Oncology, The First Affiliated Hospital of China Medical University , Shenyang, China
                Author notes

                Edited by: Gaurav Malviya, University of Glasgow, United Kingdom

                Reviewed by: Lutao Du, Second Hospital of Shandong University, China; Hidemi Toyoda, Mie University, Japan; Cinzia Fionda, Sapienza University of Rome, Italy

                *Correspondence: Xiangjiao Meng mengxiangjiao@ 123456126.com

                This article was submitted to Molecular Diagnostics and Therapeutics, a section of the journal Frontiers in Molecular Biosciences

                Article
                DOI: 10.3389/fmolb.2020.608404
                PMC ID: 7817973
                PubMed ID: 33490104
                SO-VID: 5776020c-7f0a-415f-9ebd-3011b61c1f88
                Copyright © Copyright © 2021 Zhao, Ma, Feng, Huang, Meng and Yu.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                Date received : 01 October 2020
                Date accepted : 07 December 2020
                Page count
                Figures: 7, Tables: 3, Equations: 0, References: 48, Pages: 12, Words: 6644
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81972796
                Funded by: Natural Science Foundation of Shandong Province 10.13039/501100007129
                Award ID: ZR2019MH010
                Funded by: Yantai Science and Technology Bureau 10.13039/501100011482
                Award ID: 2020YT06121070
                Categories
                Subject: Molecular Biosciences
                Subject: Original Research

                Keywords: primary small cell carcinoma of the esophagus,immunohistochemistry,cd155,tigit,prognosis
                Data availability:
                Keywords: primary small cell carcinoma of the esophagus, immunohistochemistry, cd155, tigit, prognosis

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