Multidimensional analysis of B7 homolog 3 RNA expression in small cell lung cancer molecular subtypes Journal Article
| Authors: | Gay, C. M.; Owonikoko, T. K.; Byers, L. A.; Choudhury, N. J.; Ahmed, S.; Cain, Z.; Qian, X.; Brentnall, M.; Heeke, S.; Poi, M.; Wu, S.; Rudin, C. M. |
| Article Title: | Multidimensional analysis of B7 homolog 3 RNA expression in small cell lung cancer molecular subtypes |
| Abstract: | PURPOSE: B7 homolog 3 (B7-H3) is a promising target for antibody-drug conjugates, with ifinatamab deruxtecan demonstrating an objective response rate of 54.8% in previously treated extensive-stage small cell lung cancer (SCLC). This analysis aimed to characterize B7-H3 RNA expression with reference to SCLC molecular subtypes (SCLC-A, SCLC-N, SCLC-P, and SCLC-I) and immune-related parameters. EXPERIMENTAL DESIGN: Tumor RNA expression and mutational burden for 1,721 patients with SCLC were derived from a real-world database (Caris Life Sciences). A predominant molecular subtype was assigned based on RNA expression using a gene-ratio classifier. PD-L1 expression was assessed by IHC (antibody 22C3; positive cutoff: tumor proportion score ≥1%). RESULTS: The predominant molecular subtype was SCLC-A in 848 (49.3%), SCLC-N in 202 (11.7%), SCLC-P in 142 (8.3%), SCLC-I in 291 (16.9%), and equivocal in 238 (13.8%) samples. B7-H3 expression was high and consistent among subtypes (q > 0.05), whereas DLL3 and SEZ6 expression each differed significantly (both q < 0.0001). PD-L1 positivity was similar across B7-H3 expression quartiles (range, 39.2%-46.5%). Median (95% confidence interval) B7-H3 expression was comparable between patients with and without prior immunotherapy [18.7 (16.5-21.2) and 17.3 (16.4-18.1) transcripts per million, respectively]. B7-H3 was not correlated with a T-cell signature but showed a strong correlation with HAVCR2/TIM3, CD86, PDCD1LG2/PD-L2, and M2 macrophages. CONCLUSIONS: B7-H3 showed consistent, high expression across SCLC molecular subtypes, whereas DLL3 and SEZ6 expression varied significantly. These data suggest that B7-H3-targeting antibody-drug conjugates may be active across SCLC subtypes, consistent with the high reported response rates. This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine |
| Keywords: | aged; middle aged; genetics; mutation; lung neoplasms; membrane proteins; pathology; tumor marker; lung tumor; gene expression regulation; gene expression regulation, neoplastic; immunology; signal peptide; intracellular signaling peptides and proteins; membrane protein; drug therapy; b7 antigen; small cell lung cancer; small cell lung carcinoma; programmed death 1 ligand 1; cd276 protein, human; b7 antigens; humans; human; male; female; biomarkers, tumor; cd274 protein, human; b7-h1 antigen; dll3 protein, human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 16 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-08-15 |
| Start Page: | 3476 |
| End Page: | 3482 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-3981 |
| PUBMED: | 40553459 |
| PROVIDER: | scopus |
| PMCID: | PMC12351277 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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