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犬传染性性病肿瘤治疗和预后过程中血浆无细胞 DNA 变化与赖氨酰氧化酶的关系。

Relationship between plasma cell-free DNA changes and lysyl oxidase during the treatment and prognosis of canine transmissible venereal tumors.

机构信息

Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran.

Department of Small Animal Internal Medicine, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.

出版信息

BMC Vet Res. 2022 Feb 21;18(1):76. doi: 10.1186/s12917-022-03173-z.

Abstract

BACKGROUND

Transmissible venereal tumors (TVT) are a wide range of canine tumors for which there are no effective markers to monitor the therapeutic response in real-time. Circulating biomarkers can be valuable in early cancer diagnosis and prognosis. Accordingly, this study aimed to investigate the significance of the cell-free DNA (cfDNA) and cfDNA integrity index to monitor the response of TVTs to vincristine and compare them with lysyl oxidase activity. Plasma and sera were collected from fifteen male dogs within four weeks before drug administration. The analytical method was mainly based on the quantitative polymerase chain reaction (qPCR) technique for short and long cfDNAs and lysyl oxidase activity was measured in serum.

RESULTS

The results of the cfDNA integrity index showed a significant (p < 0.05) difference in the baseline concentration compared to the second and third weeks (with cut-off values of 1.118 and 93.33% specificity). The cfDNA integrity index increased over time due to the reduction of short cfDNAs in the first week after treatment. Lysyl oxidase activity increased during the fourth week (p < 0.001), but there were no significant differences in the other weeks compared to the baseline. The ROC analysis of lysyl oxidase revealed high sensitivity (100%) and specificity (90%) on the second and third weeks compared to the baseline. Multivariate analysis between cfDNA integrity index and lysyl oxidase showed significant correlation (p < 0.05) only in baseline results.

CONCLUSIONS

Overall, short cfDNA, the cfDNA integrity index, and lysyl oxidase activity can be proposed as diagnostic biomarkers and putative prognostic candidates in TVT patients. These biomarkers can be combined with cytology to quickly diagnose TVT.

摘要

背景

传染性性病肿瘤(TVT)是一大类犬类肿瘤,目前尚无有效的标志物来实时监测其治疗反应。循环生物标志物在癌症早期诊断和预后中具有重要价值。因此,本研究旨在探讨游离 DNA(cfDNA)和 cfDNA 完整性指数在监测 TVT 对长春新碱反应中的意义,并将其与赖氨酰氧化酶活性进行比较。在给药前四周内,从 15 只雄性犬中采集血浆和血清。分析方法主要基于短 cfDNA 和长 cfDNA 的定量聚合酶链反应(qPCR)技术,以及血清中赖氨酰氧化酶活性的测量。

结果

cfDNA 完整性指数的结果显示,与第二和第三周相比,基线浓度有显著差异(p<0.05)(截断值为 1.118 和 93.33%特异性)。由于治疗后第一周短 cfDNA 减少,cfDNA 完整性指数随时间增加。赖氨酰氧化酶活性在第四周增加(p<0.001),但与基线相比,其他几周没有显著差异。赖氨酰氧化酶的 ROC 分析显示,与基线相比,第二和第三周的灵敏度(100%)和特异性(90%)较高。cfDNA 完整性指数和赖氨酰氧化酶之间的多变量分析仅在基线结果中显示出显著相关性(p<0.05)。

结论

总体而言,短 cfDNA、cfDNA 完整性指数和赖氨酰氧化酶活性可以作为 TVT 患者的诊断生物标志物和潜在的预后候选标志物。这些标志物可以与细胞学结合,快速诊断 TVT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a67a/8862336/6f4a779d13c1/12917_2022_3173_Fig1_HTML.jpg

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