Abstract
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Introduction: Elevated glycolysis is the universal metabolic alteration in malignancies, which allows us to assess tumour metabolism by 18F-FDG PET/CT. Lactate dehydrogenase A (LDHA) facilitates the glycolytic process by converting pyruvate to lactate, it has been confirmed to be high expression in multiple cancers, which is associated with cancer proliferation, invasion and migration. Fewer study researched the correlation LDHA expression with Warburg effect in DTC till now. So, this study aims to investigate the correlation between LDHA expression and glucose transporter (Glut1), glucose transporter 3 (Glut3), Ki67 and metabolic parameters of 18F-FDG PET/CT, then explore their value in prognosis prediction.
Methods: A retrospective analysis was performed on 69 consecutive patients with DTC. The data of 18F-FDG PET/CT were re-evaluated as follows: maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Immunohistochemistry assays were conducted to explore the expression of LDHA, glucose transporter (Glut1), glucose transporter 3 (Glut3), and Ki67. The primary end point was progression-free survival (PFS), determined by Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Correlations between 18F-FDG accumulation, LDHA, Glut1, Glut3, and Ki67 were assessed using Spearman’s rank correlation test. The assessment of their prognosis was conducted by Receiver Operating Characteristic curves and the Kaplan–Meier method. Univariate and binary logistic analyses were used to identify factors associated with clinical outcomes.
Results: 69 patients were enrolled in the study. the majority of patients were female (53.6%) and the median age at diagnosis was 52 years (range 11-77 years). Clinical outcomes were ultimately observable in 51 patients followed for a median of 3.5 years (range 1.0 – 30.0 years). During the follow-up, 6 (11.8%) patients died and 19 (37.3%) patients were evaluated as PD, and the median PFS was 39.0 (range 3.0 – 257.0) months. Immunochemistry analysis found expression of LDHA was correlated with GLUT3 (r= 0.343, p = 0.008), but not correlated with Glut1 and Ki67. Moreover, LDHA expression was positively correlated with SUVmax (r = 0.401, p = 0.002). 29 patients (42.6%) had high levels of SUVmax ( ≥ 4.7), while 40 (57.9%) patients with SUVmax < 4.7. The median LDHA scores were 270 and 180 for the high and low SUVmax groups respectively, with a significant difference between the two groups (p < 0.001). Ki67 was also significantly correlated with SUVmax (r = 0.322, p = 0.040). LDHA, Glut1, Glut3, and ki67 of one slide were not associated with the PFS, while SUVmax ≥4.7 (p = 0.001), SUVmean ≥ 3.3 (p = 0.005), MTV ≥ 35.6 cm3(p = 0.001), and TLG ≥ 144.6 cm3(p = 0.007) led to unfavorable PFS of DTC. In multivariate analysis, SUV max (OR = 13.22, 95%CI 1.23-86.77, p = 0.016) was the independent predictive factor for PD.
Conclusions: As an important kinase of Warburg effect, LDHA expression is confirmed to have positively correlation with Glut3 expression and SUVmax of 18F-FDG accumulation. Although the immunochemistry of LDHA expression does not reflect the prognosis in this study, it may be interpreted as one slide of lesion can neither represent the whole tumor, nor all lesions in the body. On the other side, it indicates 18F-FDG -uptake parameters are more reliable for evaluating prognosis in DTC.
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