Researchers discover ‘highly effective’ new biomarker for lung cancer in human trials.


Survival rates for patients with lung cancer increase dramatically the earlier the disease is diagnosed, underscoring the need for effective biomarkers that can be used for detection. Now, scientists at The Wistar Institute have found a protein that circulates in the blood that appears to be more accurate at detecting non-small cell lung cancer (NSCLC) than currently available methods used for screening.  The opensource study is published in the journal Oncotarget.

The team state that if the accuracy of this biomarker can be confirmed in a larger trial, this could lead to the development of a simple blood test that could be used for annual screening. They believe that this blood test would be easier to use, more accurate and less invasive than low-dose computed tomography (LDCT) scans, the method for lung cancer screening currently recommended by the U.S. Preventive Services Task Force (USPSTF). They go on to add that because of its accuracy, it could also better distinguish between benign lung tumours that do not pose a threat and malignant tumours that have the potential to grow and spread.

The team state that lung cancer is the leading cause of cancer deaths in both men and women in the United States. However, the five-year survival rate increases dramatically if the disease is caught and treated early. According to the American Cancer Society, if NSCLC is caught in its earliest stage, the five-year survival rate is 49 percent. However, patients who are diagnosed when the disease has metastasized, meaning that it has spread to other organs, have only about a 1 percent chance of achieving survival after five years.

In 2013, the USPSTF recommended annual screening to patients at least 55 years old who had a history of smoking and are therefore considered at high risk for developing lung cancer. Previous studies have shown that this method of screening is considered invasive and relatively expensive while not being highly accurate or widely available on a global scale.  The team state that there are many people who stand to benefit from a better diagnostic test for lung cancer and if a simple blood test can be developed that’s more accurate than low-dose CT scans, which can detect the cancer earlier with a less expensive, less invasive and more accurate blood test. Everyone stands to gain from such a test becoming available.

In the current study the team focused on cancer testis antigens (CTAs), since they are often found in tumour cells that circulate in the blood. After analyzing 116 different CTAs, the researchers identified the protein AKAP4 as a potential biomarker that could effectively distinguish between patients with and without NSCLC.

The researchers then tested AKAP4 as a biomarker in a pilot cohort that contained 264 blood samples from patients with NSCLC and 135 control samples. Of the 264 NSCLC samples, 136 samples were from patients who received a stage I diagnosis. The researchers analyzed the effectiveness of the biomarker by looking at the area under the curve (AUC), a method that calculates the ability of the test to distinguish those with disease from those without it. An AUC value of 1 means that the test perfectly distinguishes between the patients who have and don’t have a particular disease.

When the researchers compared all 264 of the NSCLC samples with the 135 control samples, the AUC was 0.9714. When the researchers looked at only the 136 samples with known stage I disease, the AUC was 0.9795. While the researchers noted that the presence of AKAP4 increased with the stage of the disease, AKAP4 was still detectable in the samples with early stage disease.

The results show that AKAP4 appears to be a highly effective biomarker for the detection of non-small cell lung cancer. If the team are able to confirm these results in a more robust study, then there is the potential for a new, more accurate screening method that could help save many, many lives.

With the positive results of this study the team will conduct a larger study with a goal of analyzing at least 800 samples. Multiple hospitals have agreed to provide blood samples for analysis to Wistar for this next study.

The team surmise that they have found a target that could result in a more accurate test than any method that’s been used to screen for non-small cell lung cancer to date.  They go on to add that with the government recommending annual screening for high-risk populations, the identification of a promising target like AKAP4 comes at a critical time. Early detection is needed in order to have a meaningful impact on this devastating disease.

Source:  The Wistar Institute 

 

Circulating Tumor Cells © 2015 SRI International.

Circulating Tumor Cells © 2015 SRI International.

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