WCLC 2025 - Posters & ePosters-P1.11.57 Association Between CD274 (PD-L1) Gene Expression and PD-L1 Immunohistochemistry in Non-Small Cell Lung Cancer Specimens

P1.11.57 Association Between CD274 (PD-L1) Gene Expression and PD-L1 Immunohistochemistry in Non-Small Cell Lung Cancer Specimens

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This study explores the correlation between CD274 (PD-L1) gene expression (GE) and PD-L1 protein expression assessed by immunohistochemistry (IHC) in non-small cell lung cancer (NSCLC) specimens. Using a cohort of 295 NSCLC patients, the researchers analyzed matched RNA GE and PD-L1 IHC results from clinical testing conducted between June and September 2024. PD-L1 IHC scores were reported using Tumor Proportion Score (TPS), categorized into three groups: TPS <1%, 1-49%, and ≥50%. CD274 expression was quantified via RNA sequencing as normalized transcripts per million (TPM).<br /><br />Results showed a significant positive correlation between CD274 GE and PD-L1 IHC TPS categories, with marked differences in gene expression distribution across the TPS groups (p < 0.001). Additionally, CD274 expression effectively predicted high PD-L1 IHC (TPS ≥50) with an area under the ROC curve (AUC) of 0.91, indicating excellent predictive performance. This correlation persisted across various clinicogenomic subgroups, including different oncogenic driver statuses such as KRAS mutations. Factors associated with PD-L1 protein levels were also linked to differences in CD274 GE.<br /><br />Clinicogenomic analysis revealed that NSCLC driver mutation status, especially KRAS mutations, showed significant association with PD-L1 expression levels. The study suggests that CD274 mRNA measurement could serve as a surrogate or complementary screening tool where limited tumor tissue restricts IHC testing, potentially guiding patient selection for anti-PD-(L)1 therapies. For example, CD274 GE might differentiate patients suitable for combination chemo-immunotherapy (TPS ≥1) versus immune checkpoint blockade alone (TPS ≥50).<br /><br />In conclusion, the research supports CD274 GE as a promising biomarker correlating with PD-L1 protein expression, advocating further investigation on clinically relevant expression thresholds. This proof-of-principle highlights gene expression profiling as an efficient alternative or adjunct to traditional IHC in guiding NSCLC immunotherapy decisions.

Asset Subtitle

Richard Huang

Meta Tag

Speaker Richard Huang

Topic Metastatic Non-small Cell Lung Cancer – Immunotherapy

Keywords

CD274 gene expression

PD-L1 protein expression

non-small cell lung cancer

immunohistochemistry

Tumor Proportion Score

RNA sequencing

clinicogenomic analysis

KRAS mutations

biomarker

immunotherapy guidance