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
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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