AKAP4 Identified as Accurate Biomarker for the Detection of Early Stage Lung Cancer

An initial survey identified the protein AKAP4 (A-kinase anchor protein 4) as a potential biomarker that could effectively distinguish between patients with and without non-small-cell lung cancer (NSCLC).

The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. In addition, AKAP4, which normally is localized to the sperm flagellum and may be involved in the regulation of sperm motility, is one of the cancer testis antigens (CTAs) that are widely expressed in tumor tissues, circulating tumor cells (CTCs), and in cancer derived exosomes that are frequently engulfed by lymphoid cells.

Investigators at The Wistar Institute (Philadelphia, PA, USA) examined the possibility that tumor-derived CTA mRNAs could be detected in the total RNA pool obtained from purified peripheral blood mononuclear cells (PBMC) of NSCLC patients. To this end, they assayed for the expression of 116 CTAs in PBMC RNA.

Results pointed to the protein AKAP4 as a potential NSCLC biomarker. The investigators validated the usefulness of AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLC patients and 135 controls from two different sites including a subset of controls with high risk lung nodules.

When all 264 lung cancer patients were compared with all 135 controls, the area under the curve (AUC) was 0.9714. When 136 stage I NSCLC lung cancers were compared with all controls, the AUC was 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 increased significantly with tumor stage but was independent 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.

"The results of this study exceeded our expectations," said senior author Dr. Qihong Huang, associate professor in the tumor microenvironment and metastasis program at The Wistar Institute. "AKAP4 appears to be a highly effective biomarker for the detection of non-small cell lung cancer. If we are able to confirm these results in a more robust study, then we have the potential for a new, more accurate screening method that could help save many, many lives. There are many people who stand to benefit from a better diagnostic test for lung cancer. If we can develop a simple blood test that is more accurate than low-dose CT scans, we 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."

The NSCLC biomarker paper was published in the May 13, 2015, online edition of the journal Oncotarget.

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