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| Name | Class |
|---|---|
| IRCCS Ospedale San Raffaele | OTHER |
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Tumor cell plasticity (TCP) is a conubium of processes which lead to re-activation of developmental programs correlating with epithelial-to-mesenchymal transition, and ultimately leading to acquisition of stem cell properties and transdifferentiation potential. Little is known about the molecular mechanisms governing TCP in lung adenocarcinoma (LUAD), i.e. the most frequent lung cancer subtype. The investigators recently identified prognostic 7-miRNAs/10-mRNAs signatures which accurately identified aggressive LUAD among patients with early-stage disease (Stage I). Furthermore, the investigators showed that such tumors show TCP features i.e. mesenchymal and stem-cell traits, high-metastatic potential. Here, the investigators aim to explore by RNAseq and by immunophenotyping at a single-cell level (scRNAseq/AbSeq), the molecular features of aggressive LUAD to unveil the mechanisms triggering TCP. The investigators predict thier results will be relevant for the development of more effective therapeutic protocols for management of aggressive LUAD.
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Analysis of diagnostic biomarkers | Other | The investigators will analyze TCP-biomarkers diagnostic by IHC, qRT-PCR and next-generation sequencing, in tumor and plasma samples of lung cancer patients. |
| Measure | Description | Time Frame |
|---|---|---|
| TCP-biomarkers screening in a prospective cohort of lung cancer patients | The investigators will: i) deconvolute the tumor epithelial cell heterogeneity of lung adenocarcinoma (LUAD) by coupling immunophenotype screening and single-cell RNAseq profiling of human LUAD samples; ii) identify subsets of LUAD cells with "active" tumor cell plasticity (TCP) using both our miRNA/RNA prognostic signatures, the C1-LUAD geneset (N=330), and previously identified signatures of lung cells high-cell plasticity (HCP) state; iii) explore the molecular features of TCP cell subsets by gene-network rewiring, pathway reconstruction analysis, and functional validation experiments of molecular "HUBs" controlling TCP pathways. Biomarkers of TCP will be also prioritized among TCP-hallmark genes and validated by immunohistochemistry (IHC/FACS) in human LUAD. | 36 months |
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Inclusion Criteria:
Exclusion Criteria:
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patients undergoing surgery for confirmed diagnosis of lung adenocarcinoma
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Fabrizio Bianchi, PhD | Contact | +390882416571 | f.bianchi@operapadrepio.it |
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D018450 | Disease Progression |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |