bims-meluca 2019-03-31 papers

Asian Pac J Cancer Prev. 2019 Mar 26. 20(3): 733-736

Prognostic and Predictive Role of Angiogenic Markers in Non- Small Cell Lung Cancer

Objective: Despite the existence of detailed consensus guidelines, challenges remain regarding the role angiogenetic factors on non-small cell lung cancer (NSCLC). This study was conducted to determine the role of the vascular endothelial growth factor (VEGF), interleukin-8 (IL-8) and angiopoietin2 (Ang2) in patients with NSCLC. Methods: This study included 64 consecutive patients with non-small cell lung cancer, who admitted to clinic. Pre-treatment serum VEGF, IL-8 and Ang2 levels were evaluated. Patients were treated according to internationally accepted guidelines. Results: VEGF and IL-8 serum levels of patients with both squamous cell carcinoma and adenocarcinoma were significantly higher than controls (p<0.05). In addition, IL-8 levels were lower among treatment-responders than non-responders (p:0.031). Impact of elevated or decreased levels of VEGF, Ang2 and IL-8 on survival was evaluated, accepting median level as reference. There was no correlation between the serum levels of VEGF, Ang2, IL-8 and survival. Conclusion: We found that the levels of angiogenic markers were significantly different between non-small cell lung cancer patients and controls. These markers could elicit more information related to stage and prognosis.

Keywords: Non-small cell lung cancer; angiogenesis; stage; prognosis

Metabolomics. 2019 Mar 25. 15(4): 52

UPLC-MS-based metabolomics reveals metabolic dysregulation in ALDH1A1-overexpressed lung adenocarcinoma cells.

Wang Y, Wang CH, Zhang YF, Zhu L, Lei HM, Tang YB.

INTRODUCTION: Specific oncogenotypes can produce distinct metabolic changes in cancer. Recently it is considered that metabolic reprograming contributes heavily to drug resistance. Aldehyde dehydrogenase 1A1 (ALDH1A1), is overexpressed in drug resistant lung adenocarcinomas and may be the cause of acquired drug resistance. However, how ALDH1A1 affects metabolic profiling in lung adenocarcinoma cells remains elusive.OBJECTIVE: We sought to investigate metabolic alterations induced by ALDH1A1 in lung adenocarcinoma in order to better understand the reprogramming and metabolic mechanism of resistance induced by ALDH1A1.
METHODS: Metabolic alterations in lung adenocarcinoma HCC827-ALDH1A1 cells were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). HCC827-ALDH1A1 metabolic signatures were extracted by univariate and multivariate statistical analysis. Furthermore, metabolite enrichment analysis and pathway analysis were performed using MetaboAnalyst 4.0 software.
RESULTS: Twenty-two metabolites were positively identified using authentic standards, including uridine monophosphate (UMP), uridine diphosphate (UDP), adenosine diphosphate (ADP), malic acid, malonyl-coenzyme A, nicotinamide adenine dinucleotide (NAD), coenzyme A and so on. Furthermore, metabolic pathway analysis revealed several dysregulated pathways in HCC827-ALDH1A1 cells, including nucleotide metabolism, urea cycle, tricarboxylic acid (TCA) cycle, and glycerol phospholipid metabolism etc. CONCLUSION: Lung cancer is the most frequent cause of cancer-related deaths worldwide. Nearly all patients eventually undergo disease progression due to acquired resistance. Mechanisms of biological acquired resistance need to be identified. Our study identified altered metabolites in HCC827-ALDH1A1 cells, enhancing our knowledge of lung adenocarcinoma metabolic alterations induced by ALDH1A1, creating a novel therapeutic pathway. These metabolic signatures of ALDH1A1 overexpression may shed light on molecular mechanisms in drug-resistant tumors, and on candidate drug targets. Furthermore, new molecular targets may provide the foundation for potential anticancer strategies for lung cancer therapy.

Keywords: ALDH1A1; Cell metabolic profiling; Lung adenocarcinoma; Tumor resistance; UPLC–QTOF-MS

DOI: https://doi.org/10.1007/s11306-019-1514-5

BMC Cancer. 2019 Mar 29. 19(1): 289

The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma.

Guo CY, Zhu Q, Tou FF, Wen XM, Kuang YK, Hu H.

BACKGROUND: The prognostic value of PKM2 and its correlation with tumour cell PD-L1 in lung adenocarcinoma (LUAD) is unclear.METHODS: 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.
RESULTS: 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).
CONCLUSIONS: Our results demonstrated that PKM2 regulated PD-L1 expression and was associated with poor outcomes in lung adenocarcinoma patients.

Keywords: Lung adenocarcinoma; Prognostic factor; Programmed death ligand 1; Pyruvate kinase M2

DOI: https://doi.org/10.1186/s12885-019-5519-2