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Background: Assessment of the immune status of muscle-invasive bladder cancer (MIBC) has previously shown to be prognostically relevant after treatment with curative intent. We conducted this study to develop a clinically applicable immune gene expression assay to predict prognosis and adjuvant chemotherapy benefit.
Patients And Methods: Gene expression of , and , immune cell (IC) populations including stromal tumor infiltrating lymphocytes (sTILs), T-cells, natural killer cells (NK-cells), macrophages, Programmed cell death protein 1 positive (PD-1) IC and tumor subtypes (MD Anderson Cancer Center/MDACC-approach) were assessed in 187 MIBC patients (Comprehensive Cancer Center Erlangen-EMN/CCC-EMN-cohort). A gene expression signature was derived by hierarchical-clustering and validated in The Cancer Genome Atlas (TCGA)-cohort. IC populations in the TCGA cohort were assessed via CIBERSORT. Benefit of platinum-containing adjuvant chemotherapy was assessed in a pooled cohort of 125 patients. Outcome measurements were disease specific survival, disease-free survival and overall survival.
Results: The gene expression signature of , and correlates with quantitative amounts of specific IC populations and sTILs (CCC-EMN: ρ-range: 0.44-0.74; TCGA: ρ-range: 0.56-0.82) and allows stratification of three different inflammation levels (inflamed high, inflamed low, uninflamed). Highly inflamed tumors are preferentially basal subtype and show favorable 5-year survival rates of 67.3% (HR=0.27; CCC-EMN) and 55% (HR=0.41; TCGA). Uninflamed tumors are predominantly luminal subtypes and show low 5-year survival rates of 28% (CCC-EMN) and 36% (TCGA). Inflamed tumors exhibit higher levels of PD-1 and Programmed cell death 1 ligand 1 (PD-L1). Patients undergoing adjuvant platinum-based chemotherapy with 'inflamed high' tumors showed a favorable 5-year survival rate of 64% (HR=0.27; merged CCC-EMN and TCGA cohort).
Conclusion: The gene expression signature of , and can assess the immune status of MIBC and stratify the survival of MIBC patients undergoing surgery and adjuvant platinum-based chemotherapy. Furthermore, the assay can identify patients with immunological hot tumors with particular high expression of PD-L1 potentially suitable for immunotherapy.
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http://dx.doi.org/10.1136/jitc-2019-000162 | DOI Listing |
Plant Cell Physiol
November 2024
Environmental Horticulture Department, University of Florida, PO Box 110670, Gainesville, FL 32611, USA.
NAC [NO APICAL MERISTEM (NAM), ARABIDOPSIS TRANSCRIPTION ACTIVATOR FACTOR 1/2 (ATAF1/2), and CUP-SHAPED COTYLEDON (CUC2)] transcription factors are key regulators of plant growth, development, and stress responses but were also crucial players during land plant adaptation and crop domestication. Using representative members of green algae, bryophytes, lycophytes, gymnosperms, and angiosperms, we expanded the evolutionary history of NAC transcription factors to unveil the relationships among members of this gene family. We found a massive increase in the number of NAC transcription factors from green algae to lycophytes and an even larger increase in flowering plants.
View Article and Find Full Text PDFPlant Mol Biol
December 2024
Institute of Botany, Jiangsu Province and Chinese Academy of Sciences, Nanjing, 210014, China.
Dioscorea alata, a key tuber crop for global food security, is threatened by anthracnose disease caused by Colletotrichum gloeosporioides. However, identification of functional resistance genes against C. gloeosporioides in D.
View Article and Find Full Text PDFHistochem Cell Biol
December 2024
Department of Stem Cells and Regenerative Medicine, Institute for Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Pajoohesh Blvd., P.O. Box 14965-161, Tehran, Iran.
METTL3, an m6A methyltransferase, is integral to the regulation of messenger RNA (mRNA) biogenesis, degradation, and translation through the N6-methyladenosine (m6A) modification. Alterations in m6A homeostasis have been implicated in the development, progression, invasion, and metastasis of certain cancers. The present research aims to examine the consequences of METTL3 knockdown using short hairpin RNA (shRNA) on the proliferation and invasive capabilities of human colorectal and melanoma cancer cell lines.
View Article and Find Full Text PDFDermatol Ther (Heidelb)
December 2024
Department of Cell Biology and Physiology, The Neuroscience Center, College of Life Sciences, Brigham Young University, Provo, UT, 84602, USA.
Introduction: Retinol has a long history of treating skin conditions, including photoaging. However, skin irritation with repeated use of retinol is well documented. The present study assessed the effectiveness of a novel topical formulation, referred to as retinol topical formulation (RTF), to improve the quality of skin health.
View Article and Find Full Text PDFEnviron Sci Technol
December 2024
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
Exposure to perfluorooctanoic acid (PFOA) and hexafluoropropylene oxide dimer acid (HFPO-DA) was associated with adipogenesis. However, potential mechanisms remain to be elucidated. Herein, a 3T3-L1 adipocyte model was used to explore the dynamic changes in adipocyte differentiation (2, 4, and 8 days) under PFOA and HFPO-DA exposure.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!