Subunits of ARID1 serve as novel biomarkers for the sensitivity to immune checkpoint inhibitors and prognosis of advanced non-small cell lung cancer
Autor: | Hong Li, Shihai Liu, Yan Zhu, Helei Hou, Lu Tian, dantong sun, Yang Wo, Qiaoling Liu |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Oncology Male Cellular immunity Lung Neoplasms ARID1A NSCLC 0302 clinical medicine Carcinoma Non-Small-Cell Lung lcsh:QD415-436 Genetics (clinical) Prognosis DNA-Binding Proteins Gene Expression Regulation Neoplastic Treatment Outcome 030220 oncology & carcinogenesis Molecular Medicine DNA mismatch repair Female Research Article medicine.medical_specialty Antigen presentation lcsh:Biochemistry 03 medical and health sciences Immune checkpoint inhibitors Internal medicine Genetics medicine Biomarkers Tumor Humans Lung cancer Molecular Biology Neoplasm Staging business.industry lcsh:RM1-950 Cancer Nomogram medicine.disease Immune Checkpoint Proteins Molecular medicine Survival Analysis ARID1B Nomograms Protein Subunits 030104 developmental biology lcsh:Therapeutics. Pharmacology Mutation business Transcription Factors |
Zdroj: | Molecular Medicine Molecular Medicine, Vol 26, Iss 1, Pp 1-9 (2020) |
ISSN: | 1528-3658 |
Popis: | IntroductionPatients with advanced non-small cell lung cancer (NSCLC) benefit from treatment with immune checkpoint inhibitors (ICIs). Biomarkers such as programmed death-ligand 1 (PD-L1), the tumor mutational burden (TMB) and the mismatch repair (MMR) status are used to predict the prognosis of ICIs therapy. Nevertheless, novel biomarkers need to be further investigated, and a systematic prognostic model is needed for the evaluation of the survival risks of ICIs treatment.MethodsA cohort of 240 patients who received ICIs from the cBioPortal for Cancer Genomics was evaluated in this research. Clinical information and targeted sequencing data were acquired for analyses. The Kaplan-Meier plot method was used to perform survival analyses, and selected variables were then confirmed by a novel nomogram constructed by the “rms” package of R software.ResultsSeven percent of the NSCLC patients harboredARID1Amutations, while 4% of the NSCLC patients harboredARID1Bmutations. Mutations inARID1AandARID1Bwere confirmed to be associated with sensitivity to ICIs. Patients harboring these mutations were found to have a better response to treatment (ARID1A:P = 0.045;ARID1B:P = 0.034) and prolonged progression-free survival (ARID1B:P = 0.032). Here, a novel nomogram was constructed to predict the prognosis of ICIs treatment. Elevation of the TMB, enhanced expression of PD-L1 and activation of the antigen presentation process and cellular immunity were found to be correlated withARID1AandARID1Bmutations.ConclusionARID1A and ARID1B could serve as novel biomarkers for the prognosis and sensitivity to ICIs of advanced NSCLC. |
Databáze: | OpenAIRE |
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