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Updated: Aug 8, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
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ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among

Jun Lu1,2,3, Yanwei Zhang1, Yuqing Lou1

  • 1Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Frontiers in Genetics
|September 24, 2021
PubMed

Insights

Ubiquitin-like conjugation gene mutations predict atezolizumab response in non-small cell lung cancer (NSCLC). Patients with these mutations had shorter survival, but the predictor showed promise in specific subgroups, especially in TP53-negative cohorts.

Area of Science:

  • Oncology
  • Genetics
  • Immunotherapy

Background:

  • Atezolizumab is approved for non-small cell lung cancer (NSCLC), but biomarkers for patient selection are needed.
  • Ubiquitin-like conjugation (UBL) biological process genes are implicated in cancer development and progression.

Purpose of the Study:

  • To investigate the utility of UBL gene mutation status as a predictive biomarker for atezolizumab response in NSCLC patients.
  • To identify patient subgroups where UBL mutation status is a more effective predictor.

Main Methods:

  • Analysis of ctDNA profiling and clinical data from 399 NSCLC patients treated with atezolizumab.
  • Integration of mutation status of key UBL genes (ABL1, APC, LRP6, FUBP1, KEAP1, TOP2A) with clinical characteristics.
  • Validation of predictive performance in independent cohorts, including TP53-negative subgroups.

Main Results:

  • UBL mutation positivity (UBL [+]) was associated with male sex and smoking history.
  • UBL (+) patients exhibited significantly shorter progression-free survival (PFS) and overall survival (OS) compared to UBL (-) patients.
  • The UBL mutation status demonstrated stronger predictive value in smokers and patients with ≤ 3 metastases, and particularly in TP53-negative cohorts.

Conclusions:

  • UBL biological process gene mutation status serves as a potential predictive biomarker for atezolizumab therapy in NSCLC.
  • This biomarker can aid in identifying NSCLC patients likely to respond to atezolizumab and potentially other immune checkpoint inhibitors.
  • Further stratification using UBL mutation status may optimize patient selection for immunotherapy in NSCLC.
Keywords:
NSCLCUBLatezolizumabbiomarkerimmune checkpoint inhibitors

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