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      PTPRD mutation is a prognostic biomarker for sensitivity to ICIs treatment in advanced non-small cell lung cancer

      research-article
      1 , 2 , 3 ,
      Aging (Albany NY)
      Impact Journals
      NSCLC, PTPRD, immune checkpoint inhibitors, nomogram, TCGA

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          Abstract

          Background: Immune checkpoint inhibitors (ICIs) have become the standard treatment for advanced non-small cell lung cancer (NSCLC). ICIs can provide durable responses and prolong survival for some patients. With the increasing routine of next-generation sequencing (NGS) in clinical practice, it is essential to integrate prognostic factors to establish novel nomograms to improve clinical prediction ability in NSCLC with ICIs treatment.

          Methods: Clinical information, response data, and genome data of advanced NSCLC treated ICIs were obtained from cBioPortal. The top 20 gene alterations in durable clinical benefit (DCB) were compared with those genes in no durable benefit (NDB). Survival analyses were performed using the Kaplan-Meier plot method and selected clinical variables to develop a novel nomogram.

          Results: The mutation of PTPRD was significantly related to progression free survival (PFS) and overall survival (OS) in advanced NSCLC with ICIs treatment (PFS: p = 0.0441, OS: p = 0.0086). The PTPRD mutation was closely related to tumor mutational burden (TMB) and tumor-infiltrating immune cells (TIICs). Two novel nomograms were built to predict the PFS and OS of advanced NSCLC patients with ICIs treatment.

          Conclusions: Our study suggested that PTPRD mutations could serve as a predictive biomarker for the sensitivity to ICIs treatment and PFS and OS in advanced NSCLC with ICIs. Our systematic nomograms showed great potential value in clinical application to predict the PFS and OS for advanced NSCLC patients with ICIs.

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          Most cited references44

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          Gene Ontology: tool for the unification of biology

          Genomic sequencing has made it clear that a large fraction of the genes specifying the core biological functions are shared by all eukaryotes. Knowledge of the biological role of such shared proteins in one organism can often be transferred to other organisms. The goal of the Gene Ontology Consortium is to produce a dynamic, controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing. To this end, three independent ontologies accessible on the World-Wide Web (http://www.geneontology.org) are being constructed: biological process, molecular function and cellular component.
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            Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer

            Pembrolizumab is a humanized monoclonal antibody against programmed death 1 (PD-1) that has antitumor activity in advanced non-small-cell lung cancer (NSCLC), with increased activity in tumors that express programmed death ligand 1 (PD-L1).
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              Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.

              Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti-PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti-PD-1 therapy. Copyright © 2015, American Association for the Advancement of Science.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                30 August 2023
                18 August 2023
                : 15
                : 16
                : 8204-8219
                Affiliations
                [1 ]Department of Radiation Oncology, Huadong Hospital, Fudan University, Shanghai 200433, P.R. China
                [2 ]Department of Medical Oncology, Shanghai Pulmonary Hospital and Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai 200433, P.R. China
                [3 ]Department of Oncology, Jiujiang University Affilliated Hospital, Jiujiang 332000, P.R. China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Chaohui Leng; email: huposetang@i.smu.edu.cn
                Article
                204964 204964
                10.18632/aging.204964
                10497019
                37602864
                c303036d-6bfa-468e-9a34-306db0cf53ff
                Copyright: © 2023 Ren et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 02 May 2023
                : 06 July 2023
                Categories
                Research Paper

                Cell biology
                nsclc,ptprd,immune checkpoint inhibitors,nomogram,tcga
                Cell biology
                nsclc, ptprd, immune checkpoint inhibitors, nomogram, tcga

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