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      DNA Damage Repair-Related Genes Signature for Immune Infiltration and Outcome in Cervical Cancer

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          Abstract

          Background: The mechanism of DNA damage repair plays an important role in many solid tumors represented by cervical cancer.

          Purpose: The purpose of this study was to explore the effect of DNA damage repair-related genes on immune function of patients with cervical cancer, and to establish and evaluate a prognosis model based on DNA damage repair-related genes.

          Methods: In the study, we analyzed the genes related to DNA damage and repair, and obtained two subtypes (F1 and F2). We selected two groups of samples for different selection, and studied which pathways were enriched expression. For different subtypes, the immune score was explored to explain immune infiltration. We got the key genes through screening, and established the prognosis model through the key genes. These 11 key genes were correlated with the expression of common Clusters of Differentiation (CD) genes in order to explore the effects of these genes on immunity.

          Results: Through the Least absolute shrinkage and selection operator (LASSO) method, we screened 11 genes from 232 candidate genes as the key genes for the prognosis score. Through the Kaplan-Meier method, four genes (HAP1, MCM5, RNASEH2A, CETN2) with significant prognostic significance were screened into the final model, forming a Nomogram with C-index of 0.716 (0.649–1.0).

          Conclusion: In cervical cancer, DNA damage repair related genes and immune cell infection characteristics have certain association, and DNA damage repair related genes and immune cell infection characteristics can effectively predict the prognosis.

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

          Hyuna Sung, Jacques Ferlay, Rebecca Siegel … (2021)
          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.
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            The immune contexture in human tumours: impact on clinical outcome.

            Wolf Herman Fridman, Franck Pagès, Catherine Sautès-Fridman … (2012)
            Tumours grow within an intricate network of epithelial cells, vascular and lymphatic vessels, cytokines and chemokines, and infiltrating immune cells. Different types of infiltrating immune cells have different effects on tumour progression, which can vary according to cancer type. In this Opinion article we discuss how the context-specific nature of infiltrating immune cells can affect the prognosis of patients.
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              The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy

              Jonathan Havel, Diego Chowell, Timothy Chan (2019)
              Checkpoint inhibitor-based immunotherapies that target cytotoxic T lymphocyte antigen 4 (CTLA4) or the programmed cell death 1 (PD1) pathway have achieved impressive success in the treatment of different cancer types. Yet, only a subset of patients derive clinical benefit. It is thus critical to understand the determinants driving response, resistance and adverse effects. In this Review, we discuss recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, PD1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome. We focus on recently identified molecular and cellular determinants of response. A better understanding of how these variables cooperate to affect tumour-host interactions is needed to optimize the implementation of precision immunotherapy.
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                Author and article information

                Contributors
                Journal
                Journal ID (nlm-ta): Front Genet
                Journal ID (iso-abbrev): Front Genet
                Journal ID (publisher-id): Front. Genet.
                Title: Frontiers in Genetics
                Publisher: Frontiers Media S.A.
                ISSN (Electronic): 1664-8021
                Publication date (Electronic): 03 March 2022
                Publication date Collection: 2022
                Volume: 13
                Electronic Location Identifier: 733164
                Affiliations
                [1] 1 Department of Radiology , Shengjing Hospital of China Medical University , Shenyang, China
                [2] 2 Department of Surgical Oncology , The First Affiliated Hospital of China Medical University , Shenyang, China
                Author notes

                Edited by: Marcelo R. S. Briones, Federal University of São Paulo, Brazil

                Reviewed by: Zitong Li, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Australia

                Vaibhav Shukla, Texas A&M University, United States

                *Correspondence: Hongzan Sun, sunhongzan@ 123456126.com

                This article was submitted to Computational Genomics, a section of the journal Frontiers in Genetics

                Article
                Publisher ID: 733164
                DOI: 10.3389/fgene.2022.733164
                PMC ID: 8927729
                PubMed ID: 35309134
                SO-VID: 5062dc2e-9782-45db-afbc-55d57c4e4d76
                Copyright © Copyright © 2022 Wang, Xu and Sun.
                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 : 29 June 2021
                Date accepted : 08 February 2022
                Categories
                Subject: Genetics
                Subject: Original Research

                ScienceOpen disciplines: Genetics
                Keywords: cervical cancer,immune infiltration,dna damage repair,prognosis biomarker,tcga
                Data availability:
                ScienceOpen disciplines: Genetics
                Keywords: cervical cancer, immune infiltration, dna damage repair, prognosis biomarker, tcga

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