title: AKAP4 is a circulating biomarker for non-small cell lung cancer.
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.
authors.affiliation: The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: Kiranmai
authors.initials: K
authors.lastname: Gumireddy
authors.affiliation: The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: Anping
authors.initials: A
authors.lastname: Li
authors.affiliation: Center for Cancer Research and Genomic Medicine, The Valley Hospital, Paramus, NJ 07652, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Chang
authors.affiliation: The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.affiliation: The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Kossenkov
authors.affiliation: University of Washington Medical Center, Seattle, WA 98195, USA.
authors.forename: Jinchun
authors.initials: J
authors.lastname: Yan
authors.affiliation: Department of Surgery, The Valley Hospital, Ridgewood, NJ 07450, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Korst
authors.affiliation: Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System, Newark, DE 19713, USA.
authors.forename: Brian T
authors.initials: BT
authors.lastname: Nam
authors.affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Center for Research on Early Detection and Cure of Ovarian Cancer, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Cancer Research and Genomic Medicine, The Valley Hospital, Paramus, NJ 07652, USA.|Department of Surgery, The Valley Hospital, Ridgewood, NJ 07450, USA.
authors.forename: Ganepola A P
authors.initials: GA
authors.lastname: Ganepola
authors.affiliation: The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Showe
authors.affiliation: The Wistar Institute Cancer Center, Philadelphia, PA 19104, USA.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Huang
mesh_terms: D054758:A Kinase Anchor Proteins / Q000097:blood*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012372:ROC Curve; D012680:Sensitivity and Specificity
chemical_list: D054758:A Kinase Anchor Proteins; C485480:AKAP4 protein, human; D014408:Biomarkers, Tumor
keywords: cancer; circulating biomarker