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Research article
Dantong Sun
the Affiliated Hospital of Qingdao University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8759-8935
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Introduction Patients 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.
Methods A 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.
Results Seven percent of the NSCLC patients harbored ARID1A mutations, while 4% of the NSCLC patients harbored ARID1B mutations. Mutations in ARID1A and ARID1B were 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 with ARID1A and ARID1B mutations.
Conclusion ARID1A and ARID1B could serve as novel biomarkers for the prognosis and sensitivity to ICIs of advanced NSCLC.
Keywords
ARID1A, ARID1B, NSCLC, immune checkpoint inhibitors, prognosis
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View the published article at Molecular Medicine.
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Reviewer #2 agreed
On 01 Aug, 2020
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Editorial decision: Accept
On 01 Aug, 2020
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On 31 Jul, 2020
Review #1 received
Received 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
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Invitations sent on 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 24 Jul, 2020
Review #2 received
Received 23 Jul, 2020
Reviewer #2 agreed
On 06 Jul, 2020
Review #1 received
Received 04 Jul, 2020
Reviewers invited
Invitations sent on 24 Jun, 2020
Reviewer #1 agreed
On 24 Jun, 2020
Editor invited
On 10 Jun, 2020
Editor assigned
On 10 Jun, 2020
Submission checks complete
On 03 Jun, 2020
First submitted
On 30 May, 2020
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Subject Areas
Molecular Biology
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A new preprint design is coming!
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See the published version of this preprint at Molecular Medicine.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Dantong Sun
the Affiliated Hospital of Qingdao University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-8759-8935
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Molecular Medicine.
Version 2
Posted 06 Aug, 2020
No community comments so far
Reviewer #2 agreed
On 01 Aug, 2020
Review #2 received
Received 01 Aug, 2020
Editorial decision: Accept
On 01 Aug, 2020
Reviewer #1 agreed
On 31 Jul, 2020
Review #1 received
Received 31 Jul, 2020
Editor assigned
On 29 Jul, 2020
Reviewers invited
Invitations sent on 29 Jul, 2020
Submission checks complete
On 28 Jul, 2020
Editor invited
On 28 Jul, 2020
No comments provided
Editorial decision: Minor revision
On 24 Jul, 2020
Review #2 received
Received 23 Jul, 2020
Reviewer #2 agreed
On 06 Jul, 2020
Review #1 received
Received 04 Jul, 2020
Reviewers invited
Invitations sent on 24 Jun, 2020
Reviewer #1 agreed
On 24 Jun, 2020
Editor invited
On 10 Jun, 2020
Editor assigned
On 10 Jun, 2020
Submission checks complete
On 03 Jun, 2020
First submitted
On 30 May, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Molecular Biology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Molecular Medicine.
Introduction Patients 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.
Methods A 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.
Results Seven percent of the NSCLC patients harbored ARID1A mutations, while 4% of the NSCLC patients harbored ARID1B mutations. Mutations in ARID1A and ARID1B were 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 with ARID1A and ARID1B mutations.
Conclusion ARID1A and ARID1B could serve as novel biomarkers for the prognosis and sensitivity to ICIs of advanced NSCLC.
Figure 1
Figure 2
Figure 3
Figure 4
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