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. 2022 Jun;13(6):14204-14214.
doi: 10.1080/21655979.2022.2084423.

Potential roles of serum ATPase and AMPase in predicting diagnosis of colorectal cancer patients

Mengchen Shi  1   2 , Yu Tian  1   2 , Lingyuan He  1   2 , Jingdan Zhang  1   2 , Xiangling Yang  1   2 , Huanliang Liu  1   2
Affiliations

Potential roles of serum ATPase and AMPase in predicting diagnosis of colorectal cancer patients

Mengchen Shi et al. Bioengineered. 2022 Jun.

Abstract

Colorectal cancer (CRC) is a common gastrointestinal cancer with high incidence and mortality rates. CRC may be associated with regulation of circulating nucleotides. This study aimed to evaluate the serum levels of nucleotide-metabolizing enzymes (ATPase and AMPase) in patients with CRC and to explore the clinical diagnostic value of these enzymes. The gene set variation analysis (GSVA) score of the ATP-adenosine signature was calculated using tumor samples from The Cancer Genome Atlas (TCGA). ATP-adenosine signaling plays a central role in CRC progression. A total of 135 subjects, including 87 patients with CRC and 48 healthy controls, were included. The serum levels of ATPase and AMPase in the CRC group were significantly higher than those in the control group (P < 0.05). Furthermore, ATP and AMP hydrolysis levels significantly increased in the advanced CRC group (P < 0.05). ATP and AMP hydrolysis was decreased by the ENTPDase inhibitors (POM-1 and ARL67156) and CD73 inhibitor (APCP). The sensitivities of ATPase and AMPase were 95.4% and 75.9%, respectively, which were higher than those of CEA (67.8%) and CA19-9 (72.4%). The specificities of ATPase and AMPase were 69.9% and 73.9%, respectively, which were higher than that of CA19-9 (47.8%). The combination of CEA, ATPase, and AMPase demonstrated high sensitivity (92.0%) and specificity (87.0%). Collectively, ATPase and AMPase activities are upregulated in CRC with considerable diagnostic significance. The combination of CEA, ATPase, and AMPase may provide a novel approach for CRC screening.

Keywords: AMP; ATP; Colorectal cancer; diagnosis; hydrolysis; nucleotide.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

None
Graphical abstract
Figure 1.
Figure 1.
ATP-adenosine signaling levels vary across tumor types of TCGA.
Figure 2.
Figure 2.
Association of the four-gene score with CRC in the GSE39582 dataset. (a) Violin plot of four-gene (ENTPD1, ENTPD2, ALPP, NT5E) score in normal tissues and CRC tissues (P < 0.05). (b) Kaplan–Meier survival plot of comparison between low four-gene score and high four-gene-score groups for overall survival (P < 0.05).
Figure 3.
Figure 3.
Levels of serum biomarkers in CRC patients and healthy controls. Levels of serum CEA (a), CA19-9 (b), ATPase (c) and AMPase (d) were elevated in 87 CRC patients compared with 48 healthy controls (*P < 0.05, ***P < 0.001).
Figure 4.
Figure 4.
Serum ATPase and AMPase levels are increased in advanced CRC patients. (a, b) The serum ATPase and AMPase levels were upregulated in 47 advanced CRC patients compared with 40 early CRC patients (*P < 0.05).
Figure 5.
Figure 5.
Effect of specific inhibitors of ENTPDases and CD73 on ATPase and AMPase levels in CRC patients. (a) Effect of specific inhibitors of ENTPDases (ARL67153 and POM-1) on ATP hydrolysis (***P < 0.001). (b) Effect of specific inhibitor of CD73 (APCP) on AMP hydrolysis (***P < 0.001).
Figure 6.
Figure 6.
ROC curves of using CEA, CA19-9, ATPase and AMPase alone in CRC patients.
Figure 7.
Figure 7.
ROC curves of using CEA, CA19-9, ATPase and AMPase in combination in CRC patients.
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