About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
patients diagnosed with lung adenocarcinoma
treatment naive
undergoing primary surgery
Disqualifiers
patients with a previous history of cancer
previously treated by chemio/immuno/radio-therapy
Trial population
patients undergoing surgery for confirmed diagnosis of lung adenocarcinoma
Trial design
Cohort
Prospective
Treatments tested in this trial
Analysis of diagnostic biomarkers
Other interventionThe investigators will analyze TCP-biomarkers diagnostic by IHC, qRT-PCR and next-generation sequencing, in tumor and plasma samples of lung cancer patients.
Treatment groups
Trial outcomes
Primary outcomes
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.
Locations
Sponsors and contacts
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Casa Sollievo della Sofferenza IRCCS
Lead sponsor
IRCCS Ospedale San Raffaele
Collaborator
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