Dysregulation of the C/EBPa Pathway in Human Lung Cancer and Search for New Biomarkers and/or Therapeutic Targets

NCT01619501 | Unknown

• 1 other identifier: 2012/00117
• Study Type: observational
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this research is to enhance the investigators understanding of the pathways involved in lung cancer, and to identify new biomarkers and/or therapeutic targets. By comparing gene expression between normal lung tissue and tumors growing in lung-specific C/EBPa KO mice, the investigators have identified the Bmi-1 proto-oncogene as being abnormally upregulated in C/EBPa-deleted tumors. Subsequently, the investigators have validated this observation in human lung cancer, implicating the investigators KO mice are an effective discovery tool for lung cancer research. Through similar approaches, the investigators have already identified (Sonic Hedgehog, SHH), and plan to identify other pathways which are abnormally regulated in C/EBPa-/- tumors. In parallel, the investigators will proceed to define the clinical relevance of the SHH pathway and the other newly-discovered molecular aberrations, by analyzing their expression and correlate it to C/EBPa expression on the samples of patients with NSCLC at NUHS. If the investigators preliminary data on Bmi-1 will be confirmed, this proto-oncogene may generate useful correlates that could be used in diagnosis and treatment of lung cancer, as well as identify new prognostic/predictive markers in lung cancer. Similarly, SHH pathway-components may behave as potential biomarkers and therapeutic tools for C/EBPa-related lung cancers. This proposal seeks to test the hypothesis that pathways which are dysregulated in lung tumors growing in a lung-specific C/EBPa KO model can be utilized as discovery tools to identify genes involved in human lung cancer pathogenesis.

Conditions

Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Define the C/EBPa-Bmi-1 axis in human lung cancer

  Tissue microarrays will be created from the lung tumours. Only resection specimens will be used for TMA construction, and small, limited biopsies will not be used. Tissue punches of 1.5mm in diameter will be cut from the blocks (2 punches per tumour, 1 punch for normal lung). Hence the rest of the tumour block is not used, preserving most of the tumour tissue in the tissue blocks, for future diagnostic use.

Secondary Outcomes (2)

• Validate the relevance of the C/EBPa-SHH pathway in human NSCLC

• Identify new downstream targets of C/EBPa in murine lung cancer and test their involvement in human pathogenesis

Eligibility Criteria

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

Study Population

Archived samples from the Department of Pathology (for IHC, FISH) and the Tissue Repository (for fresh tumor samples) at NUHS

You may qualify if:

• Patients with lung cancer

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

Nationa University Hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Ross Soo

CONTACT

+65 6779 5555; Ross_Soo@nuhs.edu.sg

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2012
• First Posted: June 14, 2012
• Study Start: April 1, 2012
• Primary Completion: March 1, 2014
• Last Updated: December 11, 2013

Record last verified: 2013-12

Locations

SG (1)