Vilfan Maša, Lampreht Tratar Urša, Milevoj Nina, Nemec Svete Alenka, Čemažar Maja, Serša Gregor, Tozon Nataša
Veterinary Faculty, University of Ljubljana, 1000 Ljubljana, Slovenia.
Institute of Oncology Ljubljana, 1000 Ljubljana, Slovenia.
Animals (Basel). 2024 Jan 29;14(3):438. doi: 10.3390/ani14030438.
Electrochemotherapy (ECT) in combination with the gene electrotransfer of interleukin 12 (IL-12 GET) has been successfully used in veterinary medicine for the treatment of mast cell tumours (MCT), but the biomarkers that could predict response to this treatment have not yet been investigated. The aim of this study was to determine the plasma nucleosome and serum ferritin concentrations, as well as the lactate dehydrogenase (LDH) activity, in the serum of treated patients before and one and six months after treatment to evaluate their utility as potential biomarkers that could predict response to the combined treatment. The study was conducted in 48 patients with a total of 86 MCTs that we treated with the combined treatment. The blood samples used for analysing the potential predictive biomarkers were taken before treatment and one and six months after treatment, when the response to treatment was also assessed. The Nu. Q Vet Cancer Test, the Canine Ferritin ELISA Kit, and the RX Daytona+ automated biochemical analyser were used to analyse the blood samples. The results showed that the plasma nucleosome concentration (before treatment (BT): 32.84 ng/mL (median); one month after treatment (1 M AT): 58.89 ng/mL (median); = 0.010) and serum LDH activity (BT: 59.75 U/L (median); 1 M AT: 107.5 U/L (median); = 0.012) increased significantly one month after treatment and that the increase correlated significantly with the presence of a more pronounced local reaction (necrosis, swelling, etc.) at that time point for both markers (nucleosome: BT (necrosis): 21.61 ng/mL (median); 1 M AT (necrosis): 69.92 ng/mL (median), = 0.030; LDH: BT (necrosis): 54.75 U/L (median); 1 M AT (necrosis): 100.3 U/L (median), = 0.048). Therefore, both the plasma nucleosome concentration and serum LDH activity could serve as early indicators of the effect of the treatment. In this context, the serum ferritin concentration showed no significant predictive potential for treatment response ( > 0.999 for all comparisons). In conclusion, this study provides some new and important observations on the use of predictive biomarkers in veterinary oncology. Furthermore, it emphasises the need for the continued identification and validation of potential predictive biomarkers in dogs with MCT and other malignancies undergoing ECT treatment in combination with IL-12 GET to ultimately improve treatment outcomes.
电化学疗法(ECT)联合白细胞介素12基因电转染(IL-12 GET)已成功应用于兽医学中治疗肥大细胞瘤(MCT),但尚未对可预测该治疗反应的生物标志物进行研究。本研究的目的是测定治疗前以及治疗后1个月和6个月时治疗患者血清中的血浆核小体和血清铁蛋白浓度,以及乳酸脱氢酶(LDH)活性,以评估它们作为可预测联合治疗反应的潜在生物标志物的效用。本研究对48例患者共86个MCT进行了联合治疗。用于分析潜在预测生物标志物的血样在治疗前、治疗后1个月和6个月采集,同时评估治疗反应。使用Nu. Q Vet癌症检测试剂盒、犬铁蛋白ELISA试剂盒和RX Daytona +自动生化分析仪分析血样。结果显示,治疗后1个月血浆核小体浓度(治疗前(BT):32.84 ng/mL(中位数);治疗后1个月(1 M AT):58.89 ng/mL(中位数);P = 0.010)和血清LDH活性(BT:59.75 U/L(中位数);1 M AT:107.5 U/L(中位数);P = 0.012)显著升高,且两种标志物在该时间点的升高均与更明显的局部反应(坏死、肿胀等)显著相关(核小体:BT(坏死):21.61 ng/mL(中位数);1 M AT(坏死):69.92 ng/mL(中位数),P = 0.030;LDH:BT(坏死):54.75 U/L(中位数);1 M AT(坏死):100.3 U/L(中位数),P = 0.048)。因此,血浆核小体浓度和血清LDH活性均可作为治疗效果的早期指标。在此背景下,血清铁蛋白浓度对治疗反应无显著预测潜力(所有比较P > 0.999)。总之,本研究为兽医学肿瘤学中预测生物标志物的应用提供了一些新的重要观察结果。此外,它强调了在接受ECT联合IL-12 GET治疗的患有MCT和其他恶性肿瘤的犬中,持续鉴定和验证潜在预测生物标志物的必要性,以最终改善治疗结果。