Research at French National Institute of Health and Medical Research (Inserm) suggests that a patient's own immune response may be more important than the tumor type in determining disease prognosis
The study profiled the expression levels of colon cancer patients' adaptive immune response-related genes using technologies from Applied Biosystems.
Traditionally, tumours are categorised according to their size and other characteristics, such as extent of invasion.
It is generally believed that the larger the tumor, the more aggressive the cancer and, therefore, the worse the patient's prognosis.
However, there is new evidence from genetic profiling and immunohistochemical studies of human colorectal tumours that the patient's own immune response may have a far greater influence on survival than expected and is a better prognostic predictor than the classically used methods.
If confirmed by additional studies, these findings could have clinical value by leading to the development of new immunotherapies that stimulate the patient's immune system to attack invading cancer cells.
These findings were presented by Prof Wolf-Herman Fridman, director of the Cordeliers Research Center, Inserm, Paris, at the annual meeting of the American Association for Cancer Research (AACR) in Los Angeles, USA, on 16 April 2007.
Scientists at the Cordeliers Research Center, Inserm analysed primary tumours from early stage colorectal cancer patients and discovered different expression patterns of immune response-related genes, according to their outcome over a period of up to 15 years.
Patients with good recovery showed increased expression levels of genes that are involved in the adaptive immune response, such as cytotoxic mediators produced by T cells, but patients with poor prognoses did not show such a strong response.
"We can clearly see major genetic differences between those patients with good prognoses and those with poor prognoses using quantitative gene expression assays," said Jerome Galon, research scientist at the Cordeliers Research Center Inserm.
"Franck Pages, assistant professor at the European Georges Pompidou Hospital, a co-contributor in this research, and I have confirmed our findings using a number of different approaches and we are very confident in the importance of the patient's adaptive immune response within the primary tumour and its affect on survival".
The researchers used the Applied Biosystems TaqMan low density arrays and 7900HT fast real-time PCR system to detect gene expression levels.
Real-time PCR is a laboratory method used to simultaneously detect and determine the amount of nucleic acid present in a sample.
This information helps scientists assess precisely how changes in the amounts of certain DNA or RNA sequences can contribute to biological processes, such as disease development.
"The TaqMan arrays and gene expression assays are easy-to-use, economical tools that are ideally suited for profiling gene signatures in complex diseases such as cancer," said Lars Holmkvist, Applied Biosystems president for Europe.
"The new findings from Inserm are an example of research enabled by Applied Biosystems technology that brings us closer to the era of personalised medicine, which aims to provide tailored treatments for individual patients that ultimately will achieve better response rates and improved chances of recovery".
Galon and his colleagues are pursuing a number of follow-up studies with Applied Biosystems gene expression technology, including an investigation of microRNA expression patterns in patients, to identify further biomarkers that doctors can use to predict prognosis for patients with colorectal, breast, prostate and lung cancer.
