BackgroundImmune checkpoint blockade (ICB) therapy has brought remarkable clinical benefits to patients with advanced non-small cell lung carcinoma (NSCLC). However, the prognosis remains largely variable.MethodsThe profiles of immune-related genes for patients with NSCLC were extracted from TCGA database, ImmPort dataset, and IMGT/GENE-DB database. Coexpression modules were constructed using WGCNA and 4 modules were identified. The hub genes of the module with the highest correlations with tumor samples were identified. Then integrative bioinformatics analyses were performed to unveil the hub genes participating in tumor progression and cancer-associated immunology of NSCLC. Cox regression and Lasso regression analyses were conducted to screen prognostic signature and to develop a risk model.ResultsFunctional analysis showed that immune-related hub genes were involved in the migration, activation, response, and cytokine-cytokine receptor interaction of immune cells. Most of the hub genes had a high frequency of gene amplifications. MASP1 and SEMA5A presented the highest mutation rate. The ratio of M2 macrophages and naïve B cells revealed a strong negative association while the ratio of CD8 T cells and activated CD4 memory T cells showed a strong positive association. Resting mast cells predicted superior overall survival. Interactions including protein–protein, lncRNA and transcription factor interactions were analyzed and 9 genes were selected by LASSO regression analysis to construct and verify a prognostic signature. Unsupervised hub genes clustering resulted in 2 distinct NSCLC subgroups. The TIDE score and the drug sensitivity of gemcitabine, cisplatin, docetaxel, erlotinib and paclitaxel were significantly different between the 2 immune-related hub gene subgroups.ConclusionsThese findings suggested that our immune-related genes can provide clinical guidance for the diagnosis and prognosis of different immunophenotypes and facilitate the management of immunotherapy in NSCLC.
The gastrointestinal stromal tumors (GIST) are a rare gastrointestinal tract malignancy. The two primary mutation sites are found in KIT and platelet-derived growth factor receptor-α (PDGFR-α) genes. The current study reports on a point mutation within the exon 11 of KIT, named KIT p.V560E. Patient-derived organoids (PDOs) are potential 3D in vitro models of tissues that can be used to identify sensitivity toward specific targets in patients with tumors and allow for personalized medicine when drugs specific for newly identified genetic locus mutations are not yet available. This study describes a 68-year-old patient who complained of diffused abdominal pain and intermittent melena lasting more than 10 days. He has no other gastrointestinal abnormalities, prior abdominal surgery, or related family history. Surgery was conducted first to remove the lesions and ascertain the disease through histology and immunohistochemical stains of the mass. Immunohistochemistry revealed that the tumor was positive for CD117 and Dog-1. Based on the above findings, he was diagnosed with GISTs. Gene detection analysis and organoid culture were then performed to verify clinical decisions. KIT p.V560E and the reduced number of RB1 copies were identified as two obvious mutations, so the patient was administrated first-line treatment of imatinib 400 mg/d. However, progressive disease prompted us to switch to sunitinib, and his condition gradually improved. Meanwhile, organoid culture showed sensitivity to sunitinib and tolerance to imatinib with half-maximal inhibitory concentration (IC50) values of 0.89 and >20, respectively. In summary, to the best of our knowledge, this is the first time that the established organoid culture indicated that the GISTs organoid could identify the sensitivity to target therapies and facilitate individual-based treatment.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.