Detection of Extracellular Protein Kinase A (ECPKA) Autoantibody in Non-Hodgkin’s Lymphoma: Its Increased Antibody Titer Decreases with a Favorable Treatment Response.
Authors: Choi Chul Won , Seo Hee Yun , Sung Hwa Jung , Yoon Soo-Young , Kim Seok Jin , Kim Byung Soo , Kim Jun Suk , Kim Meyoung-Kon 
Published: April 2020

Abstract
In cancer cells, cAMP-dependent protein kinase A (PKA) is secreted into the conditioned medium. This PKA, designated as extracellular protein kinase A (ECPKA), is markedly up-regulated in the sera of cancer patients, and surgical removal of tumors leads to decreased ECPKA levels. With the speculation that ECPKA excretion might elicit the induction of serum autoantibodies and that the presence of such autoantibodies could serve as a cancer diagnostic, a novel enzyme immunoassay (EIA) that measures IgG autoantibody against ECPKA was developed. This autoantibody was found to be elevated in patients with a wide range of active cancers, but there is no study regarding ECPKA detection in patients with non-Hodgkin’s lymphoma (NHL). We conducted this study to detect the anti-IgG autoantibody for ECPKA in sera of patients with NHL and to determine the feasibility of ECPKA autoantibody as a useful biomarker. Pathologically confirmed NHL patients who visited Guro Hospital, Korea University between February 2003 and July 2004 were enrolled. Patients were received either combination chemotherapy or radiation therapy. A total of 62 serum samples from medical students of Korea University were used as control. Serum samples were obtained before the initiation of treatment and were aliquoted and kept frozen at −80°C until thawed for this study. For patients with chemotherapy, follow-up serum samples were obtained after 4th or 6th cycle chemotherapy. Anti-ECPKA IgG autoantibodies were measured by solid-phase EIA. Total 51 patients (median age: 60) were enrolled. Antibody (Ab) titers were arbitrarily expressed as ratios to the mean absorbance of the control sera. Anti-ECPKA autoantibody titers were significantly increased in patient group than in control group (p&lt;0.001). Ab titers according to the stage (I, II vs. III, IV), IPI (0–2 vs. 3–5), LDH (normal vs. elevated) and pathology type (aggressive vs. indolent) showed no difference. Among 42 patients who took chemotherapy, both response evaluation and follow-up sampling were obtained from 31 patients. Twenty-three patients showed response to treatment (CR or PR), but 8 patients had progressive disease or early relapse. Decreased Ab titer (post-treatment) was associated with a favorable clinical response (p=0.012), and increased titer with a poor response (odds ratio = 3.45). By July 1, 2006, long-term follow-up response and survival were analyzed for 20 out of 23 patients who showed response. For patients who had decreased Ab titer at the time of treatment completion (group A), two of 13 were recurred as compared with three of 5 for those who had increased Ab titer (group B) (p=0.073). During the median follow-up period of 29 months (range: 5–37 months), total four patients died (two for group A and two for group B). The survival rate was not different between two groups. These results indicate that anti-ECPKA autoantibody is increased in patients with NHL and its titer decreases with a favorable treatment response. To determine whether ECPKA titer is associated with disease-free survival or overall survival, we plan to extend the follow-up period and to enroll more patients.