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

N/ANot Yet RecruitingNCT06409416

Casa Sollievo della Sofferenza IRCCS20 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Lung Neoplasms Progression

Interventions

The investigators will analyze TCP-biomarkers diagnostic by IHC, qRT-PCR and next-generation sequencing, in tumor and plasma samples of lung cancer patients.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

Inclusion Criteria: * patients diagnosed with lung adenocarcinoma * treatment naive * undergoing primary surgery Exclusion Criteria: * patients with a previous history of cancer * previously treated by chemio/immuno/radio-therapy

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.

Time frame: 36 months

Central Contacts

Fabrizio Bianchi, PhD

CONTACT

+390882416571 f.bianchi@operapadrepio.it

Data from ClinicalTrials.gov

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