The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear. A total of 506 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) dataset and 173 LUAD tumour tissues from Jiangxi Cancer Hospital were used to analyse the correlation between PKM2 and PD-L1 expression. We further established a stable LUAD cell line with PKM2 knockdown and confirmed the association via Western blotting and flow cytometry analysis. Moreover, the prognostic values of PKM2 and PD-L1 were evaluated by the Kaplan-Meier method and Cox proportional hazards models. Based on the above two large cohorts, we found that PKM2 was significantly positively associated with PD-L1 expression (r = 0.132, P = 0.003 and r = 0.287, P < 0.001, respectively). Subsequently, we found that PKM2 knockdown substantially inhibited PD-L1 expression in the A549 LUAD cell line. Moreover, survival analysis showed that higher expression of PKM2 was correlated with significantly shorter overall survival (OS) and disease-free survival (DFS) in lung adenocarcinoma patients (P < 0.001 and P = 0.050, respectively). Subgroup analysis showed that lung adenocarcinoma patients who expressed high PKM2 and PD-L1 levels experienced the poorest OS and DFS. Additionally, multivariate analysis suggested that high PKM2 and PD-L1 expression was an independent prognostic indicator for worse OS and DFS (HR = 1.462, P < 0.001 and HR = 1.436, P = 0.004, respectively). Our results demonstrated that PKM2 regulated PD-L1 expression and was associated with poor outcomes in lung adenocarcinoma patients.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Qian Zhu1, *, Hao Hu2, *, Feng Jiang3, *, Chang Ying Guo3, Xiong Wen Yang4, Xi Liu3 and Yu Kang Kuang2, 3 1Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong, China 2Department of Thoracic Surgery, Medical College of Nanchang University, Nanchang 330000, Jiangxi, China 3Department of Thoracic Surgery, Jiangxi Province Tumor Hospital, Nanchang 330006, Jiangxi, China 4Department of Lung Cancer Center, First People's Hospital Chenzhou, Chenzhou 423000, Hunan, China *These authors contributed equally to this work Correspondence to: Yu Kang Kuang, email: kuangyukang1@163.com Keywords: crizotinib, severe adverse effects, fatal adverse effects, non-small cell lung cancer, anaplastic lymphoma kinase Received: February 08, 2017 Accepted: June 04, 2017 Published: June 17, 2017 ABSTRACT Background: Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients. Conversely, few reports systematically analyze toxicity of crizotinib. Hence, we performed a first meta-analysis to determine the risk of crizotinib-related severe adverse events (SAEs) and fatal adverse events (FAEs) in ALK positive NSCLC patients. Materials and Methods: A systematic literature search was conducted through December 2016 to identify clinical trials that reported crizotinib monotherapy in ALK-positive NSCLC patients. Data on crizotinib-related SAEs and FAEs were extracted from each study and pooled to determine the overall incidence and risk. Random-effects or fixed-effects models were conducted to calculate the summary incidence, relative risk (RR), and 95% CIs on basis of the heterogeneity of included studies. Results: 1,924 patients from 11 clinical trials were included. The overall incidence of SAEs and FAEs with crizotinib was 19.9% (95% CI, 14.1% to 23.7%; P < 0.001) and 1.4% (95% CI, 0.9% to 2.1%; P < 0.001), respectively. Meanwhile, Asian patients have lower incidence of SAEs (11.5%, 95% CI: 7.9% to 16.5%). However, significant differences of SAEs (RR: 0.97, 95% CI, 0.79 to 1.18; P = 0.76) and FAEs (RR: 2.24, 95% CI, 0.49 to 10.30; P = 0.30) were not detected between crizotinib monotherapy and chemotherapy. Conclusions: Crizotinib may not increase the risk of SAEs and FAEs in patients with ALK positive NSCLC compared with chemotherapy.