Gene signature spots aggressive lung tumors

15 Jul

While some lung cancer screening programs are able to spot tumors in

the early stages, they do not necessarily impact patient survival. Now, a new

study that differentiates tumor type by gene expression may explain


diagram of human lungs
The researchers found 239 genes whose expression was linked to survival in patients with lung cancer.

Researchers at Oxford University in the UK and the National Cancer

Institute in Milan, Italy, report their findings in the journal


In a bid to spot developing lung cancer in the early stages, over the last

15 years, the Italian team has screened over 5,000 heavy smokers with

computed tomography (CT), an imaging procedure that uses X-rays to generate

detailed 3D pictures of the inside of the body.

The proactive screening program has been successful in that it has

picked up developing lung tumors in their early stages, spotting them more

frequently than might be expected.

However, despite these results, there has been no noticeable effect on

patient survival, says lead author Dr. Jiangting Hu, of the Nuffield Division

of Clinical Laboratory Sciences at Oxford:

“If you are doing well at finding tumors, you would expect to be reducing

deaths by treating people earlier. But there was no clear link between this

early detection and survival rates.”

Thus, Dr. Hu and colleagues set out to look at genetic differences in the

tumors that might explain why – despite early detection – some patients

survived while others did not.

Gene expression differentiates slow-growing and aggressive tumors

The team wondered if the screening program was finding mostly slow-growing

or “indolent” tumors. These could then be surgically removed, but, perhaps in

some patients, there were also some more aggressive, tumors developing that

were not picked up in the CT scans.

The researchers sampled tumors from 52 patients and compared their gene

expression signatures to clinical information about them, such as year of

detection, stage of tumor and patient survival.

The team looked at differences in gene expression because two tumors may have exactly the same genes and variants but differ in the levels of activity of certain genes. Such differences are spotted by looking at microRNA instead of DNA. MicroRNA is what converts the information in DNA into proteins.

They found 239 genes whose expression was linked to patient survival, as

senior author Francesco Pezzella, professor of tumor pathology at Oxford,


“The striking thing was that the 239-gene signature divided the

patients into two groups that clearly predicted disease-free survival and

also divided the indolent tumors detected at baseline from the tumors which

were found later on during the screening program, regardless of tumor stage

or size, and any histopathology findings from studying the


Another important finding was they could also tell which group patients

fell into based on gene expression in healthy tissue.

Perhaps an even more remarkable finding is that two members of the Milan

team also found they could spot the differences in gene signatures in blood

tests in the same patients.

Prof. Pezzella says their findings confirm there is a difference in gene expression between

slow-growing and aggressive tumors, and this can be used to identify at-risk

patients. He adds:

“The next step will be finding shorter gene signatures,

enabling us to develop more personalized diagnosis to facilitate better
-targeted cancer treatment.”

In June 2015, Medical News Today learned how another team of

researchers discovered a biomarker that could also lead to a highly accurate blood test for early

detection of nonsmall cell lung cancer – the most common form of the


Written by Catharine Paddock PhD

Copyright: Medical News Today