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Trop-2 expression in non-small cell lung cancer
Peiwen Kuo1, Emon Elboudwarej1, Marianna Zavodovskaya1
1Gilead Sciences, Inc., Foster City, California, United States of America.
Trophoblast cell-surface antigen 2 (Trop-2) is highly expressed in most non-small cell lung cancers (NSCLC). This widespread protein expression supports the use of Trop-2 targeted antibody-drug conjugates (ADCs) for NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Trophoblast cell-surface antigen 2 (Trop-2) is highly expressed in non-small cell lung cancer (NSCLC), making it a promising target for antibody-drug conjugates (ADCs).
- Understanding Trop-2 expression at the protein level is crucial for evaluating Trop-2 ADC efficacy, but current knowledge is limited.
Purpose of the Study:
- To comprehensively characterize Trop-2 expression at both mRNA and protein levels across diverse NSCLC datasets.
- To investigate the relationship between Trop-2 expression and clinical-pathological features, genetic alterations, and patient prognosis in NSCLC.
Main Methods:
- Analysis of Trop-2 mRNA, mutation, and protein expression using The Cancer Genome Atlas (TCGA) and two independent sample sets.
- Utilized immunohistochemistry (SP295 clone) and RNA sequencing for protein and RNA expression profiling.
- Correlated Trop-2 expression with clinical data, including histology, baseline characteristics, and survival outcomes.
Main Results:
- Trop-2 was highly expressed in NSCLC, with similar expression patterns observed in adenocarcinoma and squamous cell carcinoma.
- Trop-2 expression was independent of patient age, sex, tumor stage, and clinically relevant genetic alterations.
- Protein-level Trop-2 expression was detected in 82% to 90% of NSCLC cases across the analyzed sample sets.
Conclusions:
- High Trop-2 expression is a common feature across NSCLC subtypes and is not associated with prognostic factors or specific driver mutations.
- The widespread and consistent Trop-2 protein expression in NSCLC supports its broad applicability as a target for antibody-drug conjugates.
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