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, 8 (24), 39618-39626

18F-fluorodeoxyglucose Uptake Predicts PKM2 Expression in Lung Adenocarcinoma

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18F-fluorodeoxyglucose Uptake Predicts PKM2 Expression in Lung Adenocarcinoma

Ping Huang et al. Oncotarget.

Abstract

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) is widely used in the management of lung adenocarcinoma. Pyruvate kinase M2 (PKM2) plays a key role in glycolysis. We therefore investigated whether PKM2 expression affects 18F-FDG uptake in a retrospective analysis of 76 patients who underwent 18F-FDG PET/computed tomography (CT) scans for staging before surgical resection. We found that PKM2 expression was higher in tumors than peritumoral tissue (p < 0.05). Patients with high PKM2 expression had reduced overall (p < 0.05) and disease-free (p < 0.05) survival as compared to those with low PKM2 expression. Comparison of the primary tumor maximum standardized uptake value (SUVmax) between patients with high and low PKM2 expression revealed that the SUVmax was higher in primary tumors with high PKM2 expression than low PKM2 expression (p < 0.05). Multivariate analysis confirmed the association between SUVmax and PKM2 expression (p < 0.05). PKM2 status was predicted with 81.6% accuracy when the SUVmax cutoff value of 6.4. Thus,18F-FDG PET/CT is predictive of the PKM2 status in lung adenocarcinoma patients and could aid in determining therapeutic strategies.

Keywords: 18F-FDG uptake; PKM2; glycolysis; lung adenocarcinomas.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1. Immunohistochemical staining of PKM2 in lung adenocarcinoma specimens
(A) Case 1: Tumor tissue with high PKM2 expression. Case 2: Tumor tissue with low PKM2 expression. Peritumoral tissues have low PKM2 expression (×200 magnification). (B) The mean PKM2 immunohistochemical staining score in lung adenocarcinoma tissue (3.96 ± 2.91) was significantly higher than that of matched peritumoral tissue (p < 0.05) (2.14 ± 1.94).
Figure 2
Figure 2. Kaplan-Meier survival analysis of 76 patients with lung adenocarcinoma
(A) The overall survival rate in patients with high PKM2 expression was significantly lower than that of patients with low PKM2 expression. (B) The disease-free survival rate in patients with high PKM2 expression was significantly lower than that of patients with low PKM2 expression.
Figure 3
Figure 3. The relationship between PKM2 expression and SUVmax in lung adenocarcinoma
(A) The SUVmax was significantly higher in patients with high (13.39 ± 6.002) compared to low PKM2 expression (5.31 ± 4.645) (p < 0.05). (B) The SUVmax and PKM2 expression are positively correlated (r2 = 0.47, p < 0.05).
Figure 4
Figure 4. ROC curve of the SUVmax for predicting PKM2 expression
The area under the ROC curve was 0.874 ± 0.041. When the threshold of the SUVmax was set at 6.4, the sensitivity and specificity were 90.2% and 71.4%, respectively.
Figure 5
Figure 5. Relationship between SUVmax and GLUT1 and HK2 expression
(A) The SUVmax was significantly higher in tumors with high (13.6 ± 6.3) compared to low GLUT1 expression (5.3 ± 3.9) (p < 0.05). (B) There was no significant difference in SUVmax between the high and low HK2 expression groups (p > 0.05).

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