AKAP4 is a circulating biomarker for non-small cell lung cancer

// Kiranmai Gumireddy 1 , Anping Li 1 , David H. Chang 2 , Qin Liu 1 , Andrew V. Kossenkov 1 , Jinchun Yan 3 , Robert J. Korst 4 , Brian T. Nam 5 , Hua Xu 6 , Lin Zhang 7 , Ganepola A.P. Ganepola 2, 4 , Louise C. Showe 1 , Qihong Huang 1 1 The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA 2 Center for Cancer Research and Genomic Medicine, The Valley Hospital, Paramus, NJ 07652, USA 3 University of Washington Medical Center, Seattle, WA 98195, USA 4 Department of Surgery, The Valley Hospital, Ridgewood, NJ 07450, USA 5 Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA 6 Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China 7 Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, PA 19104, USA Correspondence to: Qihong Huang, e-mail: qhuang@wistar.org Keywords: circulating biomarker, cancer Received: March 13, 2015      Accepted: May 01, 2015      Published: May 13, 2015 ABSTRACT Cancer testis antigens (CTAs) are widely expressed in tumor tissues, circulating tumor cells (CTCs) and in cancer derived exosomes that are frequently engulfed by lymphoid cells. To determine whether tumor derived CTA mRNAs could be detected in RNA from purified peripheral blood mononuclear cells (PBMC) of non-small cell lung cancer (NSCLC) patients, we assayed for the expression of 116 CTAs in PBMC RNA in a discovery set and identified AKAP4 as a potential NSCLC biomarker. We validated AKAP4 as a highly accurate biomarker in a cohort of 264 NSCLCs and 135 controls from 2 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 are 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 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. AKAP4 is a highly accurate biomarker for the detection of early stage lung cancer.