INFO: Proteomic profiling shown more accurate than traditional biomarkers in identifying liver cancer

[Guest guest]

Public

release date: 15-Jan-2008

[ Print Article | E-mail Article | Close Window ]

Contact: Bonnie Prescott

bprescot@...

Beth Israel

Deaconess Medical Center

Proteomic

profiling shown more accurate than traditional biomarkers in identifying liver

cancer

BOSTON – As the

incidence of liver cancer continues to grow-- fueled in large part, by rising

rates of hepatitis C infections – so too does the need for tests to help

diagnose the disease at an earlier stage. A study appearing in the January 15

issue of Clinical Cancer Research demonstrates that a novel mass-spectrometry

based form of proteomic profiling is more accurate than traditional biomarkers

in distinguishing liver cancer patients from patients with hepatitis C liver

cirrhosis, particularly with regard to identifying patients with small, curable

tumors. Led by researchers at Beth Israel Deaconess Medical Center

(BIDMC), the study could help lead to earlier diagnostic methods – and

subsequent treatments -- for liver cancer.

“Proteomics

represents a potentially powerful tool for the serologic recognition of protein

profiles associated with cancer,” explains co-senior author Towia Libermann,

PhD, Director of the Genomics Center at BIDMC and Associate Professor of Medicine at Harvard Medical School.

“Although this

particular proteomics technology, SELDI-TOF MS [surface enhanced laser desorption/ionization

time of flight mass spectrometry] had already proven capable of identifying

liver cancer in some limited studies, this was the first time that the

technology was compared side-by-side with the clinical standard biomarker in a

cohort of patients at risk for developing the disease,” adds Liebermann,

who is also Director of the Dana-Farber/Harvard Cancer Center Proteomics Core

in the Division of Interdisciplinary Medicine and Biotechnology at BIDMC.

Over a single decade,

the incidence of liver cancer (hepatocellular carcinoma) increased from 1.8 to

2.5 per 100,000 patients, in large part due to a rise in the spread of hepatitis

C virus.

“Hepatitis C has

become a tremendous public health problem,” explains co-senior author Nezam Afdhal, MD, Director of the Liver Center at

BIDMC and Associate Professor of Medicine at Harvard Medical School.

“And a significant number of hepatitis C-infected patients will go on to

develop liver cirrhosis.” Cirrhosis results when healthy tissue is

replaced by scar tissue, preventing the liver from properly functioning.

Cirrhosis itself is responsible for more than 25,000 deaths each year. But, adds

Afdhal, secondarily, cirrhosis greatly increases a person’s chances of

developing liver cancer.

“Each year,

cirrhosis patients have a two to five percent chance that their condition will

escalate to cancer,” he explains. “And the problem is that, right

now, there is no reliable means of detecting liver cancer at an early stage,

when surgical treatment is an option. Typically by the time the disease is

discovered, the cancer has advanced and treatment options become much more

limited.”

The best hope for early

detection is cancer biomarkers, serum proteins found in altered amounts in

blood or other body fluids. The current biomarker for liver cancer in clinical

use is alpha fetoprotein (AFP). In many cases, patients with hepatitis C

undergo routine monitoring for AFP levels as an indicator of whether tumors may

have developed in their livers.

But, as Libermann

explains, the AFP biomarker has a number of shortcomings, including false

positives and false negatives. “AFP not only fails to detect many early tumors,

but it also lacks specificity. Consequently, elevated AFP levels could be

indicators of not only cancer, but also of other liver diseases or even benign

conditions, while on the other hand, many patients with small tumors will test

negative for AFP.”

The authors, therefore,

decided to evaluate the sensitivy and specificity of SELDI-TOF MS for the

detection of liver cancer and to compare its effectiveness with AFP.

Examining serum samples

of 92 patients – including 51 patients with liver cirrhosis and 41

patients with liver cancer, and among the cancer patients, individuals with

both large and small (less than 2 cm) tumors -- by SELDI-TOF mass spectrometry,

the investigators were able to identify an 11-protein signature that accurately

discriminated between the cirrhosis and cancer patients, first in a training

set (made up of 26 cirrhosis and 20 liver cancer patients), and then again in

an independent validation set (consisting of 25 cirrhosis and 19 liver cancer

patients). The resulting diagnostic value – 74 percent sensitivity and 88

percent specificity – compared favorably with the diagnostic accuracy of

AFP (73 percent sensitivity and 71 percent specificity) as well as with two

other biomarkers currently in clinical development for liver cancer, AFP-L3 and

PIVKA-IL.

“Most

strikingly,” notes Libermann, “in patients with small tumors (less

than 2 cm), where AFP identified only three, and AFP-L3 and PIVKA-II only one

each, the 11-protein signature correctly identified seven of eight patients at

this early stage of disease.

“Biomarkers play

a major role in all aspects of personalized medicine, not only in early disease

detection, but also in outcome prediction and evaluation of therapeutic

responses,” he adds. “This study provides strong evidence that serum

contains early detection biomarkers and supports the notion that a combination

of multiple biomarkers may prove more effective than individual biomarkers for

diagnosis of liver cancer, as well as other cancers.”

###

This study was funded

by grants from the National Institutes of Health.

In addition to Libermann

and Afdhal, study coauthors include BIDMC investigators Noah Zinkin MD, and

Franck Grall, PhD, (joint first authors), Killimanagalam Bhaskar, MD, Hasan Otu,

PhD, Dimitrios Spentzos, MD, Brett Kalmowitz, MD, Meghan Wells,

Guerrero, BSc, and Asara, PhD.

Beth Israel Deaconess Medical Center is

a patient care, teaching and research affiliate of Harvard Medical School and

consistently ranks among the top four in National Institutes of Health funding

among independent hospitals nationwide. BIDMC is clinically affiliated with the

Joslin Diabetes Center and is a research partner of Dana-Farber/Harvard Cancer Center.

BIDMC is the official hospital of the Boston Red Sox. For more information,

visit www.bidmc.harvard.edu.