Liverpool Lung

Project Biobank

Dr. Mike Davies

(on behalf of Prof. John Field)

• Lung Cancer is the

biggest cause of cancer

death in the UK.

• Late presentation of the disease

is a major factor in high mortality.

• Early detection, based on risk

profiling , imaging (CT) or novel

biomarkers aim to reduce this.

• Better targeted therapies

required.

http://www.cancerresearchuk.org/cancer-info/cancerstats/mortality/cancerdeaths/#Twenty

A cancer biobank

A hospital cohort biobank (diagnostic

samples from suspected cancer patients)

A population cohort biobank (minimally

invasive samples from at-risk LLP cohort)

Samples + DATA

Research through local & international

collaborations (academia & industry).

LLP Biobank facilitates

Excellence in RESEARCH

Tissues, tumours, data

Epidemiology + Outcome data = Risk prediction

LLP Risk Model (% risk of lung cancer within 5 years)

www.mylungrisk.co.uk

UK Lung Cancer

Screening Trial

Tissues, tumours, data

Epidemiology + Outcome data = Risk prediction

Population cohort DNA = GWAS = Cancer predisposition

Blood, sputum, buccal scrapes, breath = screening

Blood, bronchial lavage, sputum = screening/diagnosis

Biopsy/resection = diagnosis/prognosis/treatment

Co

lle

ct

& s

tore

R

ecru

it

Surgical:

LHCH

Rapid Access Clinics:

LHCH, AUH, WH

COPD:

RLBUH

LLP:

GP clinics

LLP:

CRC

Tissue

Protein

DNA

RNA

microRNA

VOCs

Bio

ma

teri

al

Da

ta S

ys

tem

s

Pro

vis

ion

Process

Bronchial

Lavage

Process

Sputum

Process

Buccal

Scrape

Process

Blood

Process

Breath

Sample

Process

Frozen

Tumour

Process

Fixed

Tumour

Biomaterials and associated clinical information:

local, national and international collaboration or independent research

Information Technology:

Secure database storage

& retrieval system

Laboratory

Information

Management

System

Outcome

data: MCCR, ONS, HES

Risk model data Epidemiology data Clinical data

Infrastructure

LIMS Data

Pre-2002 Collection

Cohort Timelines

Collection Data (subjects) Biobanked Samples

Population controls 6942 121195

Hospital cohort controls 1276 10675

Lung Cancer Cases 2491 19235

Total 10709 147119

Population cohort Case Follow-up

July 1999 recruited onto LLP

Sept 2000

Aug 2001

Aug 2002

July 1999

Blood and Sputum Samples Lung Function, LLP Questionnaire

June 2003 Tumour and normal &

Blood Samples. Clinical data

June 2003 Squamous carcinoma

T2N0

May 2003 Hospital Cohort

suspected cancer

May 2003 Bronchial Lavage &

Blood Samples

Ongoing Case review, ONS & MCCR

Feb 2004 Blood

Samples

Sample Study (grant funding) Example Output

1 Blood DNA SNP GWAS validation (ILCCO) Hung Nature (2008)

2 Tumour RNA Gene expression (ALMAC, EUELC) Han Int J Onc (2012)

3 Bronchial Lavage Diagnostic DNA methylation (CRUK) Nikolaidis Can Res (2012)

4 Tumour & Normal microRNA Gene expression & diagnosis (CURELUNG) Bediaga BJC (2013)

5 Tumour & Normal DNA DNA methylation (CURELUNG) Sandoval JCO (2013)

1 2 3 4 5

Still Alive ONS Dec

2012

GWAS – blood DNA case/control cohort

Molecular diagnosis in bronchial washings

Diagnostic biomarkers – Tumour-specific miRNA

Tumour progression– Tumour mRNA

Outcome biomarkers - Tumour DNA Methylation

Cancer Genomics: NGS on Tumour & Normal DNA

Cancer Genomics: NGS on Tumour & Normal DNA

Early Detection – breath analysis EU Framework7 – LCAOS

European multicentre collaboration led by Prof Hossam Haick, Technion, Israel

• A Lung Cancer artificial olfactory sensor

• A nanotechnology-based electronic nose for

detecting Volatile Organic Compounds (VOCs).

• Analyses the exhaled breath for screening,

diagnosing and monitoring lung cancer.

• Detects cancer and discriminates between the

different stages of the disease, or different

mutations.

LLP

case-control & cohort

Biobank

Samples

Biomarker Development & validation

Molecular Epidemiology

Data

Liverpool Region Lung Cancer Alliance

LLP

case-control & cohort

Biobank

Samples

Biomarker Development & validation

Molecular Epidemiology

Data

LHCH RLBUH CCC AUT Primary Care CCG LHP

At Risk population Lung cancer patients Clinical Trials MCCRN

Early Detection

CT screening

(UKLS)

Risk Stratification

GWAS Hung Nature 2008

International Lung Cancer Consortium (ILCCO)

LLP Risk Prediction Model Annals Int Med 2012

Clinical Diagnostics Molecular profiling

Plasma Tumour tissue

Non-resectable tumours Resectable tumours

Sputum

Biopsies

Early detection: DNA methylation in biological fluids

Early detection: microRNA in biological fluids

Biomarkers of therapeutic stratification

Early detection: breath test

Genome and methylome analysis by NGS.

Prognostic biomarkers

Gene networks: redefining the molecular pathology

of NSCLC

Data sources: MCCR, ONS, HES

ACKNOWLEDGEMENTS

University of Liverpool Roy Castle Lung Cancer Research Programme

RLBUH

John Gosney

Tom Giles

LHCH

Martin Walshaw

Martin Ledson

Colin Smyth

Richard Page

John Holemans

Prof John Field

Lakis Liloglou

Research Nurses

Peris Widdows

Angela Tobin

Sarah Feeney

Angela Kenny

Administrators

Bev Green

Jan Farley

Gaynor Hunt

Rachel Boden

David Rycroft

Clinical Resources

Julie Bryan

Stephanie Unsworth

Derek Pye

Jennie Goggins

Epidemiology

Michael Marcus

Adrian Cassidy

Olaide Raji

Ying Chen

IT

Asaf Niaz

Nail Hodge

Liverpool Primary Care Trust

Sefton Primary Care Trust

Knowsley Primary Care Trust

Scientists, students, international

collaborators, funding bodies….

University

Hospital

Aintree

Paul Walker

John Sheard

Robert Angus

Chris Warburton

Peter Calverley

ACKNOWLEDGEMENTS

University of Liverpool Roy Castle Lung Cancer Research Programme

RLBUH

John Gosney

Tom Giles

LHCH

Martin Walshaw

Martin Ledson

Colin Smyth

Richard Page

John Holemans

Prof John Field

Lakis Liloglou

Research Nurses

Peris Widdows

Angela Tobin

Sarah Feeney

Angela Kenny

Administrators

Bev Green

Jan Farley

Gaynor Hunt

Rachel Boden

David Rycroft

Clinical Resources

Julie Bryan

Stephanie Unsworth

Derek Pye

Jennie Goggins

Epidemiology

Michael Marcus

Adrian Cassidy

Olaide Raji

Ying Chen

IT

Asaf Niaz

Nail Hodge

Liverpool Primary Care Trust

Sefton Primary Care Trust

Knowsley Primary Care Trust

Scientists, students, international

collaborators, funding bodies….

University

Hospital

Aintree

Paul Walker

John Sheard

Robert Angus

Chris Warburton

Peter Calverley

The Roy Castle Lung Cancer Foundation for

generous support over many years.

All those patients and population cohort

members who have so generously given

their samples, data and time to helping

lung cancer research and the LLP Biobank.