J Cancer 2020; 11(15):4442-4452. doi:10.7150/jca.42610

Research Paper

High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict worse survival in human lung adenocarcinoma

Long Long1, Mengxi Chen2, Yu Yuan2, Alex Lau Ming2, Wei Guo2, Kaisong Wu3✉, Honglei Chen1,2✉

1. Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P. R. China
2. Department of Pathology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P. R. China
3. Department of Respiratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan 430071, P. R. China

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Citation:
Long L, Chen M, Yuan Y, Ming AL, Guo W, Wu K, Chen H. High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict worse survival in human lung adenocarcinoma. J Cancer 2020; 11(15):4442-4452. doi:10.7150/jca.42610. Available from http://www.jcancer.org/v11p4442.htm

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Abstract

Background: Immunotherapy targeting PD-1/PD-L1 represents a breakthrough in the treatment of lung cancer. Pyruvate kinase M2 (PKM2) is not only a critical player in glycolysis, but also conducive to tumor progression and immune response. While both have been linked to lung adenocarcinoma (AC), the correlation and clinical significance of PKM2 and PD-L1 expression in human lung AC tissues remains not entirely explored.

Methods: Expression of PKM2 and PD-L1 proteins were detected by immunohistochemistry in 74 lung AC cases and the corresponding noncancerous tissues. Simultaneously, multiplex immunofluorescence was used to detect PKM2, PD-L1, CK, CD3, and CD68 in the lung AC tissues. We measured expression patterns and co-localization of these markers, evaluating their association with clinicopathological features and overall survival. Validation of findings was conducted using mRNA expression data from The Cancer Genome Atlas (TCGA) of 515 lung AC cases.

Results: High expression of PKM2 in tumor cells was significantly related with lymph node metastasis and TNM stage (p=0.035, p=0.017, respectively). Moreover, PKM2 expression in tumor cells was positively correlated with tumor PD-L1 expression. High expression of PKM2, PD-L1 in tumor cells and immune cells predicted high mortality rate and poorer survival rates, respectively. Additionally, multivariate Cox regression models indicated that high expression of PKM2 in tumor cells was an independent prognostic factor. Based on TCGA genomic data, high PKM2 mRNA expression was significantly associated with poorer survival (p=0.001).

Conclusion: High expression of PKM2 synergizes with PD-L1 in tumor cells and immune cells to predict poorer survival rates in patients with lung AC.

Keywords: PKM2, PD-L1, Lung adenocarcinoma, Energy metabolism, Immune checkpoint therapy