Tumor Cell Plasticity and Aggressiveness in Human Non-small Cell Lung Cancer

Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
AgeNot listed
SponsorCasa Sollievo della Sofferenza IRCCS

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 volunteers

Qualifiers

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

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Analysis of diagnostic biomarkers

    Other intervention

    The 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

No treatment groups listed

Trial outcomes

Primary outcomes

1

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.

Time frame
36 months

Secondary outcomes

Other outcomes

Locations

This trial has no locations.

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Casa Sollievo della Sofferenza IRCCS

Lead sponsor

IRCCS Ospedale San Raffaele

Collaborator

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