Genomic and immune profiling of pre-invasive lung adenocarcinoma
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ABSTRACT:
PROVIDER: EGAS00001004006 | EGA |
REPOSITORIES: EGA
Similar Datasets
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).
2020-01-30 | PXD017334 | JPOST Repository
Project description:Transcriptional profiling of human lung minimally invasive adenocarcinoma cells comparing control lepidic growth (LG) cell pool with micro-invasion (MI) cell pool.
2012-01-02 | GSE30663 | GEO
Project description:To study the evolution of DNA methylation at genome level and methylation intra-tumor heterogeneity (ITH) during early lung carcinogenesis, we performed multiregional reduced representation bisulfite sequencing (RRBS) of 62 resected lung nodules from 39 patients including atypical adenomatous hyperplasia (AAH, n=14), adenocarcinoma in situ (AIS, n=15), minimally invasive adenocarcinoma (MIA, n=22), and invasive adenocarcinoma (ADC, n=11).
| EGAS00001004610 | EGA
Project description:Transcriptional profiling of human lung minimally invasive adenocarcinoma cells comparing control lepidic growth (LG) cell pool with micro-invasion (MI) cell pool. Two-condition experiment, LG vs. MI cell pools. Biological replicates: 1 control LG cancer cell, 1 MI cancer cell in an individual MIA tumor. One replicate per array.
2012-01-02 | E-GEOD-30663 | biostudies-arrayexpress
Project description:multi-region exome sequencing of 116 pulmonary nodules including lung
preneoplasia atypical adenomatous hyperplasia (AAH, N=22), adenocarcinoma in situ (AIS,
N=27), minimally invasive adenocarcinoma (MIA, N=54) and invasive lung adenocarcinoma
(ADC, N=13).
| EGAD00001004960 | EGA
Project description:<p>Integrated proteo-genomics studies to characterize tumor heterogeneity of metastatic lung adenocarcinoma and thymic carcinoma are lacking. We carried out whole exome sequencing, RNA sequencing, copy number estimation and mass spectrometry-based proteomics of 40 tumors from five rapid/warm autopsy patients. We found highly variable mutational heterogeneity that was largely driven by APOBEC-mutagenesis with the expression of APOBEC3B (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=APOBEC3B">Gene ID: 9582</a>) and APOBEC3A_B (<a href="https://www.ncbi.nlm.nih.gov/gene/100913187">Gene ID: 100913187</a>) due to underlying APOBEC3 region germline variants as the likely mediating mechanism. APOBEC3A_B expression was associated with increased immune tumor microenvironment and CD274 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=CD274">Gene ID: 29126</a>) expression while smoking was associated with increased APOBEC-mutagenesis in TP53 (<a href="https://www.ncbi.nlm.nih.gov/gene/?term=TP53">Gene ID: 7157</a>) mutant tumors with high APOBEC3B expression. Heterogeneity at the level of the transcriptome and proteome occurred in association with copy number heterogeneity, not APOBEC-induced mutational heterogeneity. Arm and focal copy number alterations (CNAs) occurred as an evolutionarily late event in a subset of patients, with corresponding changes in the transcriptome and proteome, implicating CNAs as a driving force of heterogeneity in the evolution of metastatic disease.</p>
| phs001432 | dbGaP
Project description:DCIS is a non-invasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer while others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor intrinsic subtypes, proliferative, immune scores and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immune suppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly ncRNA and methylation profiles reproduce changes observed post-invasion. Among the most significant findings we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and specific SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a pre-invasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. RNAs from 25 out of 30 (83%) pure HG-DCIS and 10 normal breast organoids (total 35 samples) were subjected to RNA-Seq analysis by using Illumina HiSeq2000 platform Please note that description of samples employed for the NGS analyses including age, race, ER/PR immunohistochemistry results, ITIL/STIL scores and PAM50 classification is provided the 'Supplementary Data1_Samples data.xlsx' (available on Superseries record)
2015-07-25 | E-GEOD-69240 | biostudies-arrayexpress
Project description:DCIS is a non-invasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer while others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor intrinsic subtypes, proliferative, immune scores and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immune suppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly ncRNA and methylation profiles reproduce changes observed post-invasion. Among the most significant findings we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and specific SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a pre-invasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer. DNA from 24 out of 30 (80%) HG-DCIS samples and 5 normal breast organoids (total 29 samples) were subjected to reduced representation bisulfite sequencing analysis (RRBS) by using Illumina HiSeq2000 platform. Please note that description of samples employed for the NGS analyses including age, race, ER/PR immunohistochemistry results, ITIL/STIL scores and PAM50 classification is provided the 'Supplementary Data1_Samples data.xlsx' (available on Superseries record)
2015-07-25 | E-GEOD-69993 | biostudies-arrayexpress
Project description:Lung adenocarcinomas differ in prognosis based on their histologic growth pattern. Micropapillary growth in lung adenocarcinoma is associated with a host of adverse prognostic factors, especially metastases. Metastasis is the major cause of high mortality in lung cancer. Exploring the underlying mechanisms of metastasis in the early stage thus holds promise for identifying new therapeutic strategies that may enhance survival. We applied quantitative mass spectrometry to compare protein expression profiles in different histologic subtypes, including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), invasive adenocarcinoma (IAC) histologic subtype includes acinar (ACI), micropapillary (MIP). We discovered that low-density lipoprotein receptor–related protein–associated protein 1 (LRPAP1) has the highest protein level in MIP, which was confirmed by immunohistochemistry (IHC). The co-expressed proteins in our data like PSMD1 and HSP90AB1 were also reported they are high-expressed in cancer and have important role in metastasis. Overexpressed LRPAP1 promoted migration of lung cancer cells in vitro. Our findings suggest that LRPAP1 plays an important role in promoting lung cancer cell metastasis, and may act as a novel target for anti-metastatic therapy.
2022-12-07 | PXD038594 | iProX
Project description:DCIS is a non-invasive precursor lesion to invasive breast carcinoma. We still have no understanding on why only some DCIS lesions evolve to invasive cancer while others appear not to do so during the life span of the patient. Here, we performed full exome (tumor vs. matching normal), transcriptome and methylome analysis of 30 pure high-grade DCIS (HG-DCIS) and 10 normal breast epithelial samples. Sixty two percent of HG-DCIS cases displayed mutations affecting cancer driver genes or potential drivers. Mutations were observed affecting PIK3CA (21% of cases), TP53 (17%), GATA3 (7%), MLL3 (7%) and single cases of mutations affecting CDH1, MAP2K4, TBX3, NF1, ATM and ARID1A. Significantly, 83% of lesions displayed numerous large chromosomal copy number alterations, suggesting they might precede selection of cancer driver mutations. Integrated pathway-based modeling analysis of RNA-seq data allowed us to identify two DCIS subgroups (DCIS-C1 and DCIS-C2) based on their tumor intrinsic subtypes, proliferative, immune scores and in the activity of specific signaling pathways. The more aggressive DCIS-C1 (highly proliferative, basal-like or ERBB2+) displayed signatures characteristic of activated Treg cells (CD4+/CD25+/FOXP3+) and CTLA4+/CD86+ complexes indicative of a tumor-associated immune suppressive phenotype. Strikingly, all lesions showed evidence of TP53 pathway inactivation. Similarly ncRNA and methylation profiles reproduce changes observed post-invasion. Among the most significant findings we observed upregulation of lncRNA HOTAIR in DCIS-C1 lesions and hypermethylation of HOXA5 and specific SOX genes. We conclude that most HG-DCIS lesions, in spite of representing a pre-invasive stage of tumor progression, displayed molecular profiles indistinguishable from invasive breast cancer.
2015-07-25 | GSE69993 | GEO