Citations 2
Multicohort Analysis of Bronchial Epithelial Cell Expression in Healthy Subjects and Patients with Asthma Reveals Four Clinically Distinct Clusters
Lee, Ian , Ganesan, Ananthakrishnan , Kalesinskas, Laurynas , Zheng, Hong , Ahn, Haejun C., Christenson, S., Erzurum, Serpil C. , Zein, Joe , Bleecker, Eugene R., Meyers, Deborah A., Fahy, John V. , Israel, Elliot, Jarjour, Nizar N. , Moore, W., Mauger, David T. , Woodruff, Prescott G. , Ortega, Victor E. , Khatri, Purvesh , Zheng, Hong , Lee, Ian , Christenson, Stephanie A. , Castro, M , Wenzel, Sally E , Khatri, Purvesh , Lee, Ian Y , Christenson, Stephanie A , Lee, Ian , Meyers, Deborah A. , Castro, Mario , Israel, Elliot , Wenzel, Sally E. , Levy, Bruce David
American Journal of Respiratory Cell and Molecular Biology | December 19, 2024 | Volume: 73 | Issue: 1 | Pages: 73-87
Abstract Asthma is a heterogeneous disease with variable presentation and characteristics. There is a critical need to identify underlying molecular endotypes of asthma. We performed the largest transcriptomic analysis of 808 bronchial epithelial cell samples across 11 independent cohorts, including 3 cohorts from the Severe Asthma Research Program. Using seven datasets (218 patients with asthma, 148 healthy control subjects) as discovery cohorts, we identified 505 differentially expressed genes, which we validated in the remaining four datasets. Unsupervised clustering using the 505 differentially expressed genes identified four reproducible clusters of patients with asthma across all datasets, corresponding to healthy control subjects, patients with mild/moderate asthma, and patients with severe asthma with significant differences in several clinical markers of severity, including pulmonary function, Type 2 inflammation, fractional exhaled nitric oxide, and maximum bronchodilator reversibility. Importantly, we found the same clusters in pediatric patients using nasal lavage fluid cells, demonstrating the gene signature and clusters are not confounded by age and are conserved in both lower and upper airways. The four asthma clusters may represent a unifying framework for understanding the molecular heterogeneity of asthma. Further study could potentially enable a precision medicine approach of matching therapies with patients with asthma most likely to benefit.
Mutational landscape of gastric adenocarcinoma in Chinese: Implications for prognosis and therapy
Chen, Kexin , Yang, Da , Li, Xiangchun , Sun, Baocun , Song, Fengju , Cao, Wenfeng , Gao, Zhibo, Li, Haixin , Liang, Han , Zhao, Yanrui, Li, Miao , Buckner, Jan C. , Patterson, Scott D. , Reinhard, Christoph , Bhathena, Anahita, Joshi, Deepa, Wang, Yi Michael, Raghavakaimal, Sreekumar, Lü, Xin , Chang, Han , Ba, Sujuan, Luo, Longhai, Cavenee, Webster K. , Zhang, Wei , Hao, Xishan , Chen, Kexin , Buckner, Jan, Sun, Baocun , Brat, Daniel J. , Zheng, Hong , Ye, Xiang , Mischel, Paul S. , Croce, Carlo Maria , Li, Hui , Pan, Yang
Proceedings of the National Academy of Sciences | January 13, 2015 | Volume: 112 | Issue: 4 | Pages: 1107-1112
Significance We have identified a lethal subtype of gastric cancer (GC) that is characterized by high levels of clonal heterogeneity and TP53 (tumor protein P53) mutation. We have also uncovered key novel mutations in the targetable NRG1 (neuregulin-1) and ERBB4 (V-Erb-B2 avian erythroblastic leukemia viral oncogene homolog 4) ligand-receptor pair and identified BRCA2 (breast cancer 2, early onset) mutations as new genetic markers to predict better survival for GC. Our study represents a novel approach for GC personalized medicine and identified novel clinical actionable therapies for GC therapy.