Background: The effects of non-amplification short variant (SV) mutations in (programmed death-ligand 1 (PD-L1)) on PD-L1 protein expression and immune checkpoint inhibitors (ICPIs) therapy are unknown. Here, we present a retrospective analysis of mutations detected by comprehensive genomic profiling (CGP) and correlate these results with tumor-cell PD-L1 immunohistochemistry (IHC)-based expression assessment to better understand the relationship between mutations and protein expression of PD-L1.
Methods: CGP was performed on hybridization-captured, adaptor ligation-based libraries using DNA and/or RNA extracted from 314,631 tumor samples that were sequenced for up to 406 cancer-related genes and select gene rearrangements. PD-L1 IHC was performed on a subset of cases (n=58,341) using the DAKO 22C3 PD-L1 IHC assay and scored with the tumor proportion score (TPS).
Results: Overall, the prevalence of SV mutations was low (0.3%, 1081/314,631) with 577 unique variants. The most common SV mutations were R260H (n=51), R260C (n=18), R125Q (n=12), C272fs*13 (n=11), R86W (n=10), and R113H (n=10). The prevalence of mutations varied depending on tumor type with diffuse large B-cell lymphoma (1.9%, 19/997), cutaneous squamous cell carcinoma (1.6%, 14/868), endometrial adenocarcinoma (1.0%, 36/3740), unknown primary melanoma (0.9%, 33/3679), and cutaneous melanoma (0.8%, 32/3874) having the highest frequency of mutations. Of the R260H cases concurrently tested with PD-L1 IHC, most (81.8%, 9/11) had no PD-L1 expression, which contrasts to the five E237K cases where most (80%, 4/5) had PD-L1 expression. In addition, we saw a significantly lower level of PD-L1 expression in samples with a clonal truncating variant (nonsense or frameshift indel) when compared with samples with a subclonal truncating variants (mean: TPS=1 vs TPS=38; p<0.001), and also in clonal versus subclonal missense mutations (mean: TPS=11 vs TPS=22, respectively; p=0.049) CONCLUSIONS: We defined the landscape of mutations in a large cohort of tumor types that can be used as a reference for examining mutations as potential resistance biomarkers for ICPI. Furthermore, we presented novel data on the correlation of mutations and PD-L1 protein expression, providing important new information on the potential functionality of these mutations and can serve as a basis for future research.
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http://dx.doi.org/10.1136/jitc-2021-002558 | DOI Listing |
Plant Physiol Biochem
December 2024
College of Ecology and Environment, Chengdu University of Technology, Sichuan, 610059, China; Ministry of Education Key Laboratory of Cell Activities and Stress Adaptations, Lanzhou University, Lanzhou, 730000, China; Key Laboratory of Monitoring for Heavy Metal Pollutants, Ministry of Ecology and Environment, Hunan, 410019, China. Electronic address:
With the intensification of climate change coupled with the inadequate agricultural management in certain regions, plants face numerous challenges due to various abiotic stresses. Stress associated proteins (SAPs) are essential functional genes in plants for coping with stress. This research provides a functional analysis of OsSAP17, a protein belonging to the SAP family in rice.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Urology and Metabolic Rehabilitation Center, Beijing Rehabilitation Hospital, Capital Medical University, Xixia Zhuang, Badachu, Shijingshan District, Beijing, China.
Prostate cancer is epithelial malignant prostate hyperplasia caused by a tumor. We found prostate cancer GSE141551 and GSE200879 profiles from gene expression omnibus database, followed by differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis, protein-protein interaction analysis, gene function enrichment analysis, and comparative toxicology database analysis. Finally, the gene expression heat map was drawn, and miRNA information regulating core DEGs was retrieved.
View Article and Find Full Text PDFMedicine (Baltimore)
January 2025
Nerve Rehabilitation Center, Beijing Rehabilitation Hospital Affiliated to Capital Medical University, Xixia Zhuang, Badachu, Shijingshan District, Beijing, China.
Ischemic stroke is caused by blockage of blood vessels in brain, affecting normal function. The roles of Signal Transformer and Activator of Transcription 1 (STAT1), CASP8, and MYD88 in ischemic stroke and its care are unclear. The ischemic stroke datasets GSE16561 and GSE180470 were found from the Gene Expression Omnibus database.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore.
Photodynamic therapy (PDT) holds promise as a cancer treatment modality due to its potential for enhanced therapy precision and safety. To enhance deep tissue penetration and minimize tissue adsorption and phototoxicity, developing photosensitizers activated by second near-infrared window (NIR-II) light shows significant potential. However, the efficacy of PDT is often impeded by tumor microenvironment hypoxia, primarily caused by irregular tumor vasculature.
View Article and Find Full Text PDFJCO Precis Oncol
January 2025
Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.
Purpose: Fibroblast growth factor receptor 2 isoform IIIb (FGFR2b) protein overexpression is an emerging biomarker in gastric cancer and gastroesophageal junction cancer (GC). We assessed FGFR2b protein overexpression prevalence in nearly 3,800 tumor samples as part of the prescreening process for a global phase III study in patients with newly diagnosed advanced or metastatic GC.
Methods: As of June 28, 2024, 3,782 tumor samples from prescreened patients from 37 countries for the phase III FORTITUDE-101 trial (ClinicalTrials.
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