Characteristics of extracellular cyclic<scp>AMP</scp>‐dependent protein kinase as a biomarker of cancer in dogs

Bhang, Dong Ha; Choi, Ul Soo; Kim, B. G.; Lee, S.-N.; Lee, S.; Roh, Hyun-Soo; Jeon, Kee Ok; Song, Won-Suk; Youn, Hwa Young; Baek, Kwan-Hyuck

doi:10.1111/vco.12304

Cited by 5 publications

(5 citation statements)

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“…The finding of a significantly higher serum ECPKA‐Ab level in dogs with cancer in our present study (Figures and ) is consistent with our previous findings in dogs . Moreover, when the cancers were classified, as shown in Table , the ECPKA‐Ab level was found to be increased regardless of the cell of origin (Figure B) and was significantly higher in the cancer group than in the healthy group; this finding has also been reported in human patients .…”

Section: Discussionsupporting

confidence: 92%

“…ECPKA has been found to be higher in serum samples from human patients with cancer than in those from individuals without cancer, suggesting its potential as a powerful diagnostic marker of cancer in humans . In a previous study, we demonstrated a significant elevation in ECPKA levels in serum samples from dogs with cancer and suggested that ECPKA could be an important candidate diagnostic biomarker of canine malignancy . However, although ECPKA is a powerful predictor of canine cancer, it is a fragile enzyme in certain situations.…”

Section: Introductionmentioning

confidence: 80%

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Extracellular cyclic adenosine monophosphate‐dependent protein kinase A autoantibody and C‐reactive protein as serum biomarkers for diagnosis of cancer in dogs

Ryu

Kim

Choi

et al. 2018

Vet Comparative Oncology

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Protein kinase A, a cyclic adenosine monophosphate (AMP)‐dependent enzyme, normally exists within mammalian cells; however, in cancer cells, it can leak out and be found in the serum. Extracellular cyclic AMP‐dependent protein kinase A (ECPKA) has been determined to increase in the serum of cancer‐bearing dogs. However, there have been no reports in the veterinary literature on serum ECPKA autoantibody (ECPKA‐Ab) expression in dogs with cancer. The aim of this study was to evaluate ECPKA‐Ab and C‐reactive protein (CRP) as serum biomarkers for cancer in dogs. ECPKA‐Ab and CRP levels were detected by an enzyme‐linked immunosorbent assay in serum samples from dogs with malignant tumours (n = 167), benign tumours (n = 42), or non‐tumour disease (n = 155) and from healthy control dogs (n = 123). ECPKA‐Ab and CRP levels were significantly higher in the dogs with malignant tumours than in those with benign tumours or non‐tumour diseases, as well as in the healthy controls ( P < 0.001, Kruskal‐Wallis test). There was a significant positive correlation between the neoplastic index, which was developed using ECPKA‐Ab and CRP levels, and the presence of cancer in dogs ( P < 0.001); the area under the receiver‐operating characteristic curve was estimated to be >0.85 ( P < 0.001). In conclusion, ECPKA‐Ab is a potential serum biomarker for a broad spectrum of cancers. Combined measurement of CRP and ECPKA‐Ab levels in serum improves the sensitivity and accuracy of a diagnosis of cancer in dogs.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 80%

Extracellular cyclic adenosine monophosphate‐dependent protein kinase A autoantibody and C‐reactive protein as serum biomarkers for diagnosis of cancer in dogs

Ryu

Kim

Choi

et al. 2018

Vet Comparative Oncology

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“…The aim of this study was to demonstrate the increase in AniScan ECPKA antibody levels in dogs bearing malignant tumors compared to non-tumor groups and to evaluate the usefulness of this approach for detecting malignant tumors in dogs. A significantly higher ECPKA antibody level was found in various malignant tumor groups than control groups, as shown in previous studies with regard to canine malignant tumors [13,14]. In human medicine, abundant evidence shows that ECPKA activity or the ECPKA autoantibody level increases in various malignant tumors regardless of the type of tumor or location, including bladder, breast, cervical, colon, esophageal, gastric, liver, lung, ovarian, pancreatic, prostate, renal, renal cell, small bowel, rectal, and adenocystic carcinomas; melanoma; sarcoma and thymoma; liposarcoma; and leiomyosarcoma [8].…”

Section: Discussionsupporting

confidence: 84%

“…Evidence shows that the activity of ECPKA increases in various malignant tumors in human medicine [8][9][10][11], and a report demonstrated that ECPKA activity decreased after surgical removal in human melanoma patients [12]. However, although it is suggested that the ECPKA level also increases in malignant tumors in mammals other than humans, few studies regarding ECPKA are available in the veterinary literature [13,14].…”

Section: Introductionmentioning

confidence: 99%

AniScan Using Extracellular Cyclic AMP-Dependent Protein Kinase A as a Serum Biomarker Assay for the Diagnosis of Malignant Tumors in Dogs

Lee

Song

Lee³

et al. 2020

Sensors

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The early detection of tumors improves chances of decreased morbidity and prolonged survival. Serum biomarkers are convenient to use and have several advantages over other approaches, such as accuracy and straightforward protocols. Reliable biomarkers from easily accessible sources are warranted for the development of cost-effective assays for routine screening, particularly in veterinary medicine. Extracellular c-AMP-dependent protein kinase A (ECPKA) is a cytosolic leakage enzyme. The diagnostic accuracy of detecting autoantibodies against ECPKA was found to be higher than that of ECPKA activity from enzymatic assays, which use a complicated method. Here, we investigated the diagnostic significance of measuring serum ECPKA autoantibody levels using an in-house kit (AniScan cancer detection kit; Biattic, Anyang, Korea). We used sera from 550 dogs, including healthy dogs and those with malignant and benign tumors. Serum ECPKA and immunoglobulin G were determined using the AniScan cancer detection kit. ECPKA autoantibody levels were significantly higher (p < 0.01) in malignant tumors than in benign tumors, non-tumor diseases, and healthy controls. On the basis of sensitivity and specificity values, AniScan ECPKA is a rapid and easy-to-use assay that can be applied to screen malignant tumors from benign tumors or other diseases in dogs.

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“…Since this methodological approach is currently employed in determining the PKA levels in blood samples, we also included four different sera in our own analysis [ 22 , 30 ]. As expected, four out of four sera exhibited O.D.…”

Section: Resultsmentioning

confidence: 99%

Protein Kinase A Detection in Human Urine Samples

Ragone

Salzillo

Spina

et al. 2021

JCM

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Actively involved in tumor maintenance, cAMP-dependent protein kinase A (PKA) has been proposed as a putative biomarker in cancer. Recently, an active PKA form has been identified in human sera and PKA autoantibodies have been detected in cancer patients. However, their serum functions, as well as diagnostic significance, remain largely unknown. Although several PKA detection assays have been developed, none refer to a laboratory diagnostic procedure. Among these, ELISA and Western blotting (WB) assays have been employed in PKA detection. Since, to the best of our knowledge, there are no data showing its presence in human urine samples, herein, we explore the possibility of PKA’s existence in this biological specimen. Interestingly, among the 30 screened urines by quantitative sandwich ELISA, we recognized detectable PKA levels in 5 different samples, and of those two exhibited a considerable high concentration. To corroborate these results, we also evaluated PKA’s presence in both positive and negative ELISA urines by WB. Remarkably, immunoblotting analysis confirmed PKA’s existence in certain, but not in all, human urine specimens. Despite being quite preliminary, these findings firstly identify PKA in urine samples and provide evidence for its potential clinic usage as a diagnostic analyte in laboratory medicine.

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Characteristics of extracellular cyclicAMP‐dependent protein kinase as a biomarker of cancer in dogs

Abstract: Our data strongly propose that detection of serum ECPKA level is a potential and specific diagnostic tool for cancer in dogs.

Cited by 5 publications

References 28 publications

Extracellular cyclic adenosine monophosphate‐dependent protein kinase A autoantibody and C‐reactive protein as serum biomarkers for diagnosis of cancer in dogs

Extracellular cyclic adenosine monophosphate‐dependent protein kinase A autoantibody and C‐reactive protein as serum biomarkers for diagnosis of cancer in dogs

AniScan Using Extracellular Cyclic AMP-Dependent Protein Kinase A as a Serum Biomarker Assay for the Diagnosis of Malignant Tumors in Dogs

Protein Kinase A Detection in Human Urine Samples

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