AKAP4 Is a Promising Blood Biomarker For Early Detection of Lung Cancer

MedicalResearch.com Interview with:
Qihong Huang, M.D., Ph.D. Associate professor in the Tumor Microenvironment and Metastasis Program The Wistar InstituteQihong Huang, M.D., Ph.D.
Associate professor in the Tumor Microenvironment and Metastasis Program
The Wistar Institute

Medical Research: What is the background for this study? What are the main findings?

Dr. Huang: Lung cancer is the leading cause of cancer deaths in both men and women in the United States and results in more deaths globally than breast, prostate and colon cancers combined. While the five year survival rate for early stage non-small cell lung cancer (NSCLC) is above 50%, it is less than 5% in patients with metastatic disease.  Clearly, early detection can save lives, but accurate screening tests for high-risk individuals are still lacking. Although low dose computed tomography (LDCT) has been successfully used for screening in high-risk populations, multiple negative factors are associated with recurrent LDCT screening, including false-positives and false-negatives, unnecessary invasive procedures, radiation exposure, global availability of the technology and cost. Although several non-invasive tests for lung cancer using body fluids such as blood, urine or sputum are under investigation, none are currently available.

When low dose computed tomography is used for screening, patients who are 50 years old or older are frequently diagnosed with pulmonary nodules.  However, only a small fraction of the nodules detected are subsequently diagnosed as lung cancer.  In cases where it is difficult to differentiate malignant from benign nodules, it is recommended that patients with these indeterminate nodules be followed with serial LDCT, which increases radiation exposure and financial cost. A simple, inexpensive blood test that differentiates malignant from benign nodules would fill an important clinical need.

In this study, we validated AKAP4 as a highly accurate biomarker in a cohort of 264 blood samples from patients with known non-small cell lung cance and 135 controls samples from two different sites including a subset of controls with high risk lung nodules.   When all 264 lung cancers were compared with all 135 controls, the area under the ROC curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC is 0.9795, and when all lung cancer patients were compared to 27 controls with histologically confirmed benign lung nodules – a comparison of significant clinical importance – the AUC was 0.9825. AKAP4 expression increases significantly with tumor stage but independently of age, gender, smoking history or cancer subtype. Follow-up studies in a small number of resected NSCLC patients revealed a decrease of AKAP4 expression post-surgical resection that remained low in patients in remission and increased with tumor recurrence. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer, lung cancer recurrence, and distinguishing malignant from benign lung nodules.

Medical Research: What should clinicians and patients take away from your report?

Dr. Huang: AKAP4 is a promising blood biomarker for the early detection of lung cancer, recurrence, and distinguishing malignant from benign lung nodules. A total of 399 samples (264 lung cancer samples and 135 control samples) in this study is a fairly large sample size for a pilot study. However, further validation in larger sample size is needed. If the sensitivity and specificity of AKAP4 can be validated in larger cohort of patients, it would represent the best biomarker to date for cost-effective early detection of lung cancer patients. It is possible that a combination of a blood test and low-dose CT is powerful for the detection of early stage lung cancer and distinguishing malignant from benign lung nodules, thus significantly improving the survival of lung cancer patients while dramatically lowering the cost of the screening.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Huang: We will validate the findings in larger sample size. Samples will be collected from multiple hospitals. If the results from this study are validated, we will conduct clinical trials to determine the assay can be used for the detection of early stage lung cancer, lung cancer recurrence, and distinguish malignant from benign lung nodules.

Citation:

Qihong Huang et al. AKAP4 is a circulating biomarker for non-small cell lung cancer. Oncotarget, May 2015

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Qihong Huang, M.D., Ph.D., Associate professor in the Tumor Microenvironment and Metastasis Program, & The Wistar Institute (2015). AKAP4 Is a Promising Blood Biomarker For Early Detection of Lung Cancer MedicalResearch.com

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