Lung Cancer Treatment Selection Based on a Multiplexed Proteomic Assay

Limited non–small-cell lung cancer (NSCLC) tissue sections pose challenges for biomarker testing to guide therapeutic decisions.1 Genetic sequencing helps guide targeted therapy, but recent proteogenomic studies demonstrated the importance of protein expression in classifying tumor subtypes. Precision cancer treatment is primarily based on genetic sequencing rather than proteomic testing due to the lack of robust proteomic assays.2 To complement existing approaches for treatment and trial matching of lung cancer patients, a multiplexed proteomic assay was developed and evaluated in this study.2

Candidate biomarkers were selected based on known biology and clinical relevance. Using a matrix prepared from 25 NSCLC cell lines, reverse calibration curves were used to evaluate assay sensitivity, linearity, and performance. When needed, samples were reviewed by a pathologist and processed with filter-aided sample preparation.2

The multiplexed liquid chromatography-multiple reaction monitoring (LC-MRM) assay was successfully applied to NSCLC cell lines (n = 25), formalin-fixed paraffin-embedded (FFPE) specimens (n = 30), and frozen tissues (n = 108).2 The results differentiated subtypes of 25 NSCLC cell lines and frozen lung squamous-cell carcinomas (LSCC) based on the expression levels of proteins to assess tumor phenotype, cancer signaling, and immune status.2

The samples prepared from FFPE specimens with limited sizes demonstrated compatibility with biopsies. The LC-MRM data from tumor specimens were consistent with pathology evaluations. The 108 tumors from LSCC patients could be grouped into subtypes, including immune hot and immune cold tumors based on B- and T-cell markers. Quantitation of cancer antigens can also assist with the direction of immunotherapy.2

The investigators demonstrated that a highly multiplexed targeted proteomics assay can be used to quantify biomarkers in lung cancer cell lines, FFPE specimens, and frozen tumor tissues. Furthermore, the LC-MRM assay can be implemented with tumor biopsies to enable therapy selection and trial matching. A future study is planned to allow the researchers to examine the MRM assay results of 108 LSCC tissues by comparing them to previous proteogenomic results to further understand tumor biology.2


  1. Hofman P. The challenges of evaluating predictive biomarkers using small biopsy tissue samples and liquid biopsies from non-small cell lung cancer patients. J Thorac Dis. 2019;11(Suppl_1):S57-S64.
  2. Reddy S, Alontaga A, Stewart PA, et al. Multiplexed targeted proteomics of biomarkers for lung cancer treatment selection. Presented at: 2022 American Association for Cancer Research Annual Meeting; April 8-13, 2022; New Orleans, LA. Abstract LB121.

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