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

NCT06409416 | Not Yet Recruiting

• 1 other identifier: RF-2021-12372433
• Study Type: observational
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Lung Neoplasms; Progression

Outcome Measures

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.

  36 months

Interventions

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.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

patients undergoing surgery for confirmed diagnosis of lung adenocarcinoma

You may qualify if:

• patients diagnosed with lung adenocarcinoma
• treatment naive
• undergoing primary surgery

You may not qualify if:

• patients with a previous history of cancer
• previously treated by chemio/immuno/radio-therapy

Sponsors & Collaborators

• Casa Sollievo della Sofferenza IRCCS: lead
• IRCCS Ospedale San Raffaele: collaborator

MeSH Terms

Conditions

Lung Neoplasms; Disease Progression

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Fabrizio Bianchi, PhD

CONTACT

+390882416571; f.bianchi@operapadrepio.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head, cancer Biomarkers Unit

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 10, 2024
• Study Start: July 1, 2024
• Primary Completion: June 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 18, 2024

Record last verified: 2024-06