11
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Identification and validation of a prognostic signature of autophagy, apoptosis and pyroptosis-related genes for head and neck squamous cell carcinoma: to imply therapeutic choices of HPV negative patients

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          An effective tool is needed to predict the prognosis of head and neck squamous cell carcinoma (HNSCC). Human papillomavirus (HPV) positive HNSCC patients generally have a favorable survival and a promising responsiveness to radiotherapy, chemoradiotherapy and checkpoint blockades. However, HPV negative patients, the majority of HNSCC patients, have been largely overlooked. Cell death has been involved in the therapeutic resistance of cancers. To this end, we aimed to identify the association of autophagy, apoptosis and pyroptosis-related genes with the prognosis of HNSCC, and construct a prognostic signature to predict the prognosis for HNSCC, especially for HPV negative HNSCC.

          Methods

          Autophagy and apoptosis-related genes were obtained from Gene Set Enrichment Analysis (GSEA) website, and pyroptosis-related genes were obtained from GSEA and Gene Ontology (GO) database. We established the cell death index (CDI) based on RNA sequencing (RNA-seq) data and clinicopathological information from The Cancer Genome Atlas (TCGA) dataset. The prognostic value of CDI was verified by Kaplan-Meier, receiver operating characteristic (ROC) and univariate and multivariate Cox regression analyses in TCGA dataset, and validated with the datasets from Gene Expression Omnibus (GEO) and Qilu Hospital of Shandong University. We further assessed the immune microenvironment of patients with high and low CDI scores. Moreover, the expression of the signature genes in HNSCC cell lines were explored.

          Results

          We found that CDI was an independent prognostic indicator for overall survival (hazard ratio 3.80, 95% confidential interval: 2.70-5.40, P < 0.001). Furthermore, HNSCC patients with high CDI scores obtained increased overall survival post radiation indicating benefits from radiotherapy of this subgroup. On the other hand, HPV negative HNSCC patients with low CDI exhibited increased checkpoint gene expressions, an inflamed tumor microenvironment and an enriched immune response-related functions, suggesting the potential benefits from checkpoint immunotherapies of this subgroup. Moreover, we validated the baseline and induced expressions of above 16 genes in two HPV negative HNSCC cell lines, CAL27 and SCC-15.

          Discussion

          We established a prognostic signature and emphasized its implements in the therapeutic choices of HPV negative HNSCC patients, the majority and the poor outcome population of HNSCC.

          Related collections

          Most cited references42

          • Record: found
          • Abstract: found
          • Article: not found

          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Robust enumeration of cell subsets from tissue expression profiles

            We introduce CIBERSORT, a method for characterizing cell composition of complex tissues from their gene expression profiles. When applied to enumeration of hematopoietic subsets in RNA mixtures from fresh, frozen, and fixed tissues, including solid tumors, CIBERSORT outperformed other methods with respect to noise, unknown mixture content, and closely related cell types. CIBERSORT should enable large-scale analysis of RNA mixtures for cellular biomarkers and therapeutic targets (http://cibersort.stanford.edu).
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              TIMER2.0 for analysis of tumor-infiltrating immune cells

              Abstract Tumor progression and the efficacy of immunotherapy are strongly influenced by the composition and abundance of immune cells in the tumor microenvironment. Due to the limitations of direct measurement methods, computational algorithms are often used to infer immune cell composition from bulk tumor transcriptome profiles. These estimated tumor immune infiltrate populations have been associated with genomic and transcriptomic changes in the tumors, providing insight into tumor–immune interactions. However, such investigations on large-scale public data remain challenging. To lower the barriers for the analysis of complex tumor–immune interactions, we significantly improved our previous web platform TIMER. Instead of just using one algorithm, TIMER2.0 (http://timer.cistrome.org/) provides more robust estimation of immune infiltration levels for The Cancer Genome Atlas (TCGA) or user-provided tumor profiles using six state-of-the-art algorithms. TIMER2.0 provides four modules for investigating the associations between immune infiltrates and genetic or clinical features, and four modules for exploring cancer-related associations in the TCGA cohorts. Each module can generate a functional heatmap table, enabling the user to easily identify significant associations in multiple cancer types simultaneously. Overall, the TIMER2.0 web server provides comprehensive analysis and visualization functions of tumor infiltrating immune cells.
                Bookmark

                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                10 January 2023
                2022
                : 13
                : 1100417
                Affiliations
                [1] 1 Laboratory of Basic Medical Sciences, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan, China
                [2] 2 School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University , Jinan, China
                [3] 3 Shandong Key Laboratory of Oral Tissue Regeneration, Shandong University , Jinan, China
                [4] 4 Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Shandong University , Jinan, China
                [5] 5 Shandong Provincial Clinical Research Center for Oral Diseases, Shandong University , Jinan, China
                [6] 6 Department of Oral and Maxillofacial Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan, China
                [7] 7 Precision Biomedical Laboratory, Liaocheng People’s Hospital, Medical College of Liaocheng University , Liaocheng, China
                [8] 8 School of Pharmaceutical Sciences, Shandong University , Jinan, China
                [9] 9 Department of Radiation Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University , Jinan, China
                Author notes

                Edited by: Die Wang, Genentech, United States

                Reviewed by: Jia Wei Zheng, Shanghai Jiao Tong University, China; Jiyang Yu, St. Jude Children’s Research Hospital, United States; Nerina Denaro, Azienda Sanitaria Ospedaliera S.Croce e Carle Cuneo, Italy

                *Correspondence: Xun Qu, quxun@ 123456sdu.edu.cn ; Yu Dou, yu.dou@ 123456sdu.edu.cn

                This article was submitted to Systems Immunology, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2022.1100417
                9872116
                36703967
                afda1729-e597-45ea-9b24-23c8c8c8c684
                Copyright © 2023 Nan, Dou, Chen, Wang, Sun, Meng, Neckenig, Ai, Liu, Dong, Ma, Cheng and Qu

                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
                : 16 November 2022
                : 19 December 2022
                Page count
                Figures: 7, Tables: 0, Equations: 1, References: 42, Pages: 14, Words: 5128
                Funding
                This study was supported by the National Natural Science Foundation of China (NSFC) granted to YD (No.81902770) and XQ (No.81772879).
                Categories
                Immunology
                Original Research

                Immunology
                head and neck squamous cell carcinoma,human papillomavirus,autophagy,apoptosis,pyroptosis,tumor microenvironment,prognosis,radiotherapy

                Comments

                Comment on this article