Project description:We conducted a comprehensive proteogenomic analysis comprising proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas.
Project description:Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.
Project description:Lung adenocarcinoma (LUAD) radiologically displayed as subsolid nodules (SSNs) is prevalent. However, precise clinical management of SSNs requires thorough understanding of its tumorigenesis and progression. Here, we analyzed 66 LUAD displayed as SSNs covering 3 histological stages including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) by incorporating genomics, proteomics, phosphoproteomics and glycoproteomics. Intriguingly, cholesterol metabolism is aberrantly regulated in the preneoplastic AIS stage. Furthermore, sustained endoplasmic reticulum stress was demonstrated to be a hallmark and a reliable biomarker of AIS progression to IAC. Consistently, targeted promotion of ER stress profoundly retarded LUAD progression. Our study provides comprehensive proteogenomic landscape of SSNs, sheds lights on the tumorigenesis and progression of SSNs and suggests preventive and therapeutic strategies for LUAD.
Project description:The aim of the study was to investigate gene expression tumour progression of KRas*/MYC driven lung tumours from adenocarcinoma in situ to invasive disease.
Project description:Global evolution of the tumor microenvironment associated with progression from preinvasive/minimally invasive to invasive human lung adenocarcinoma
Project description:Clinical FFPE tissue proteomic analyses were performed for early lung adenocarcinomas including adenocarcinoma in-situ (AIS), minimally invasive adenocarcinoma (MIA) and lepidic predominant invasive adenocarcinoma (LPA).
Project description:To investigate changes in the tumor microenvironment (TME) during lung cancer progression, we interrogate tumors from two computer tomography (CT) defined groups. Pure non-solid (pNS) CT density nodules contain preinvasive/minimally invasive cancers and solid density nodules invasive cancers. Profiling data reveal a dynamic interaction between the tumor and its TME throughout progression. Alterations in genes regulating the extracellular matrix and genes regulating fibroblasts are central at the preinvasive state. T cell-mediated immune suppression is initiated in preinvasive nodules and sustained with rising intensity through progression to invasive tumors. Reduced T cell infiltration of the cancer cell nests is more frequently associated with preinvasive cancers, possibly until tumor evolution leads to a durable, viable invasive phenotype accompanied by more varied and robust immune suppression. Upregulation of immune checkpoints occurs only in the invasive nodules. Throughout progression an effector immune response is present but is effectively thwarted by the immune-suppressive elements.
Project description:Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis, with a 5-year survival rate of 100%. However, early invasive adenocarcinoma (EIA) often has a fatal outcome. In this study, we compared the expression profiles of AIS with those of EIA showing a fatal outcome, and screened the differentially expressed genes by cDNA microarray.