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. 2021 Oct;13(10):5691-5700.
doi: 10.21037/jtd-21-1463.

Pyruvate dehydrogenase E1α represents a reliable prognostic predictor for patients with non-small cell lung cancer resected via curative operation

Ryuichi Ito  1 , Masakazu Yashiro  2 , Takuma Tsukioka  1 , Nobuhiro Izumi  1 , Hiroaki Komatsu  1 , Hidetoshi Inoue  1 , Yurie Yamamoto  2 , Noritoshi Nishiyama  1
Affiliations

Pyruvate dehydrogenase E1α represents a reliable prognostic predictor for patients with non-small cell lung cancer resected via curative operation

Ryuichi Ito et al. J Thorac Dis. 2021 Oct.

Abstract

Background: Lung cancer is associated with a high morbidity and mortality rate worldwide; however, no reliable and independent prognostic predictor for non-small cell lung cancer (NSCLC) after curative surgery is available. Glucose metabolism is correlated with cancer cell proliferation. Pyruvate dehydrogenase E1α (PDH-E1α) catalyzes the conversion of pyruvate to acetyl-CoA and promotes aerobic glucose metabolism. In this study, we examined the relationship between PDH-E1α expression and clinicopathological factors associated with NSCLC to identify a reliable prognostic predictor of NSCLC after curative surgery.

Methods: A total of 445 patients with NSCLC who underwent curative resection were enrolled in this study. PDH-E1α expression was evaluated via immunohistochemistry. We analyzed the correlation between PDH-E1α expression and clinicopathological features of the patients.

Results: In total, 248 (56%) of the 445 patients with NSCLC were PDH-E1α-positive, and 197 patients were PDH-E1α-negative. PDH-E1α positivity was significantly correlated with the presence of adenocarcinoma (P<0.001) compared to the PDH-E1α-negative group. Patients with NSCLC showing PDH-E1α-negative expression had a significantly poorer overall survival rate (P=0.007) than those showing PDH-E1α-positive expression, especially at stage II. Patients with PDH-E1α negative expression also showed a poorer disease-free survival rate (P=0.02). Multivariate analysis revealed that PDH-E1α negativity (P=0.037) and male sex (P<0.001) were significantly correlated with a poor overall survival.

Conclusions: PDH-E1α may represent a reliable prognostic predictor for NSCLC in patients that have recently undergone curative resection, especially at stage II.

Keywords: Pyruvate dehydrogenase (PDH); curative resection; non-small cell lung cancer (NSCLC); predictive marker.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jtd-21-1463). The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Representative images of immunostaining intensity of PDH-E1α expression in patients with NSCLC. Intensity score: 0, negative; 1+, weakly positive; 2+, positive; 3+, strongly positive. Bar, 50 µm. PDH-E1α, pyruvate dehydrogenase E1α; NSCLC, non-small cell lung carcinoma.
Figure 2
Figure 2
Relationship between overall survival rate and PDH-E1α expression. The 5-year overall survival rate in 445 patients with NSCLC. Patients showing negative PDH-E1α expression have significantly poorer survival rates (P=0.007) than those showing positive PDH-E1α expression. The PDH-E1α expression in associated with the pathological stage was evaluated. A significant difference in the association of survival rate and PDH-E1α expression in pathological stage II (P=0.026) was observed, but not for stages 0–I and III. PDH-E1α, pyruvate dehydrogenase E1α; NSCLC, non-small cell lung carcinoma.
Figure 3
Figure 3
Relationship between disease-free survival rate and PDH-E1α expression. 5-year disease-free survival rate in 445 patients with NSCLC. Patients showing negative PDH expression had significantly poorer survival rates (P=0.02) than those showing positive PDH expression. No significant difference was found in the survival rate according to the PDH expression associated with pathological stage. PDH-E1α, pyruvate dehydrogenase E1α; NSCLC, non-small cell lung carcinoma.
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