ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients

ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients

Atezolizumab, an immune checkpoint inhibitor, has been approved for use in clinical practice in non-small cell lung cancer (NSCLC) patients, but potential biomarkers for response stratification still need further screening. In the present study, a total of 399 patients with high-quality ctDNA profil...

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Main Authors: Jun Lu, Yanwei Zhang, Yuqing Lou, Bo Yan, Benkun Zou, Minjuan Hu, Yanan Wang, Ya Chen, Zhengyu Yang, Huimin Wang, Wei Zhang, Baohui Han
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-09-01
Series:Frontiers in Genetics
Subjects:
UBL
biomarker
immune checkpoint inhibitors
atezolizumab
NSCLC
Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2021.723670/full
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spelling doaj-69a916bcc1064741857cdba2f246d2912021-09-07T04:32:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-09-011210.3389/fgene.2021.723670723670ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC PatientsJun Lu0Jun Lu1Jun Lu2Yanwei Zhang3Yuqing Lou4Bo Yan5Bo Yan6Benkun Zou7Minjuan Hu8Yanan Wang9Ya Chen10Zhengyu Yang11Huimin Wang12Wei Zhang13Baohui Han14Baohui Han15Baohui Han16Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaTranslational Medical Research Platform for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaClinical Research Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaShanghai Institute of Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaTranslational Medical Research Platform for Thoracic Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, ChinaAtezolizumab, an immune checkpoint inhibitor, has been approved for use in clinical practice in non-small cell lung cancer (NSCLC) patients, but potential biomarkers for response stratification still need further screening. In the present study, a total of 399 patients with high-quality ctDNA profiling results were included. The mutation status of ubiquitin-like conjugation (UBL) biological process genes (including ABL1, APC, LRP6, FUBP1, KEAP1, and TOP2A) and clinical information were further integrated. The results suggested that the patients with the clinical characteristics of male or history of smoking had a higher frequency of UBL mutation positivity [UBL (+)]; the patients who were UBL (+) had shorter progression-free survival (PFS) (1.69 vs. 3.22 months, p = 0.0007) and overall survival (8.61 vs. 16.10 months, p < 0.0001) than those patients with UBL mutation negativity [UBL (–)]; and more promising predictive values were shown in the smoker subgroup and ≤ 3 metastasis subgroup. More interestingly, we found the predictor has more performance in TP53-negative cohorts [training in an independent POPLAR and OAK cohorts (n = 200), and validation in an independent MSKCC cohort (n = 127)]. Overall, this study provides a predictor, UBL biological process gene mutation status, not only for identifying NSCLC patients who may respond to atezolizumab therapy but also for screening out the potential NSCLC responders who received other immune checkpoint inhibitors.https://www.frontiersin.org/articles/10.3389/fgene.2021.723670/fullUBLbiomarkerimmune checkpoint inhibitorsatezolizumabNSCLC
collection DOAJ
language English
format Article
sources DOAJ
author Jun Lu
Jun Lu
Jun Lu
Yanwei Zhang
Yuqing Lou
Bo Yan
Bo Yan
Benkun Zou
Minjuan Hu
Yanan Wang
Ya Chen
Zhengyu Yang
Huimin Wang
Wei Zhang
Baohui Han
Baohui Han
Baohui Han
spellingShingle Jun Lu
Jun Lu
Jun Lu
Yanwei Zhang
Yuqing Lou
Bo Yan
Bo Yan
Benkun Zou
Minjuan Hu
Yanan Wang
Ya Chen
Zhengyu Yang
Huimin Wang
Wei Zhang
Baohui Han
Baohui Han
Baohui Han
ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients
Frontiers in Genetics
UBL
biomarker
immune checkpoint inhibitors
atezolizumab
NSCLC
author_facet Jun Lu
Jun Lu
Jun Lu
Yanwei Zhang
Yuqing Lou
Bo Yan
Bo Yan
Benkun Zou
Minjuan Hu
Yanan Wang
Ya Chen
Zhengyu Yang
Huimin Wang
Wei Zhang
Baohui Han
Baohui Han
Baohui Han
author_sort Jun Lu
title ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients
title_short ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients
title_full ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients
title_fullStr ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients
title_full_unstemmed ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among TP53-Negative NSCLC Patients
title_sort ctdna-profiling-based ubl biological process mutation status as a predictor of atezolizumab response among tp53-negative nsclc patients
publisher Frontiers Media S.A.
series Frontiers in Genetics
issn 1664-8021
publishDate 2021-09-01
description Atezolizumab, an immune checkpoint inhibitor, has been approved for use in clinical practice in non-small cell lung cancer (NSCLC) patients, but potential biomarkers for response stratification still need further screening. In the present study, a total of 399 patients with high-quality ctDNA profiling results were included. The mutation status of ubiquitin-like conjugation (UBL) biological process genes (including ABL1, APC, LRP6, FUBP1, KEAP1, and TOP2A) and clinical information were further integrated. The results suggested that the patients with the clinical characteristics of male or history of smoking had a higher frequency of UBL mutation positivity [UBL (+)]; the patients who were UBL (+) had shorter progression-free survival (PFS) (1.69 vs. 3.22 months, p = 0.0007) and overall survival (8.61 vs. 16.10 months, p < 0.0001) than those patients with UBL mutation negativity [UBL (–)]; and more promising predictive values were shown in the smoker subgroup and ≤ 3 metastasis subgroup. More interestingly, we found the predictor has more performance in TP53-negative cohorts [training in an independent POPLAR and OAK cohorts (n = 200), and validation in an independent MSKCC cohort (n = 127)]. Overall, this study provides a predictor, UBL biological process gene mutation status, not only for identifying NSCLC patients who may respond to atezolizumab therapy but also for screening out the potential NSCLC responders who received other immune checkpoint inhibitors.
topic UBL
biomarker
immune checkpoint inhibitors
atezolizumab
NSCLC
url https://www.frontiersin.org/articles/10.3389/fgene.2021.723670/full
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