bims-meluca Biomed News
on Metabolism of non-small cell lung carcinoma
Issue of 2018–08–12
two papers selected by
the Muñoz-Pinedo/Nadal (PReTT) lab, L’Institut d’Investigació Biomèdica de Bellvitge and Cristina Muñoz Pinedo, L’Institut d’Investigació Biomèdica de Bellvitge
  1. 2-Deoxy-2-[fluorine-18] fluoro-d-glucose uptake on positron emission tomography is associated with programmed death ligand-1 expression in patients with pulmonary adenocarcinoma.
  2. Influence of eukaryotic translation initiation factor 6 on non-small cell lung cancer development and progression.
  1. Eur J Cancer. 2018 Aug 01. pii: S0959-8049(18)30936-5. [Epub ahead of print]101 181-190
    2-Deoxy-2-[fluorine-18] fluoro-d-glucose uptake on positron emission tomography is associated with programmed death ligand-1 expression in patients with pulmonary adenocarcinoma.
    Kyoichi Kaira, Kimihiro Shimizu, Shinsuke Kitahara, Toshiki Yajima, Jun Atsumi, Takayuki Kosaka, Yoichi Ohtaki, Tetsuya Higuchi, Tetsunari Oyama, Takayuki Asao, Akira Mogi.
      2-Deoxy-2-[fluorine-18] fluoro-d-glucose (18F-FDG) positron emission tomography (PET) is a useful modality for the assessment of tumour glucose metabolism by upregulation by hypoxia. Little is known whether the uptake of 18F-FDG within cancer cells is linked to the expression of programmed death ligand-1 (PD-L1), a predictor of anti-PD-1 antibody. We conducted a clinicopathological study to assess the expression of PD-L1 and tumour-infiltrating lymphocytes (TILs) in patients with surgically resected pulmonary adenocarcinoma (AC) who received preoperative 18F-FDG PET. A total of 315 patients with lung AC who received 18F-FDG PET were enrolled in the study. Tumour specimens were stained by immunohistochemistry for glucose transporter 1 (Glut1), hypoxia-inducible factor-1α (HIF-1α), PD-L1, CD4 and CD8. We assessed whether the uptake of 18F-FDG was correlated with clinicopathological variables. PD-L1 was highly expressed in 60% of all patients with AC, and the expression level was significantly correlated with 18F-FDG uptake, glucose metabolism and hypoxia. PD-L1 and the maximum standardised uptake value (SUVmax) were identified as independent prognostic predictors by multivariate analysis. In particular, PD-L1 could be a significant marker for predicting worse outcomes in AC patients with high 18F-FDG uptake but not in those with low 18F-FDG uptake. According to the epidermal growth factor receptor (EGFR) mutation status, the expression of PD-L1 was significantly correlated with SUVmax in patients with EGFR mutation, whereas, PD-L1 was a significant predictive negative factor in those with wild-type EGFR. 18F-FDG uptake was significantly correlated with PD-L1 expression, and the latter was closely linked to the presence of glucose metabolism and hypoxia in patients with pulmonary AC.
    Keywords:  (18)F-FDG PET; Adenocarcinoma; HIF-1α; Immunohistochemistry; Lung cancer; PD-L1
    DOI:  https://doi.org/10.1016/j.ejca.2018.06.022
  2. Eur J Cancer. 2018 Aug 01. pii: S0959-8049(18)30951-1. [Epub ahead of print]101 165-180
    Influence of eukaryotic translation initiation factor 6 on non-small cell lung cancer development and progression.
    Nadine Gantenbein, Eva Bernhart, Ines Anders, Nicole Golob-Schwarzl, Stefanie Krassnig, Christina Wodlej, Luka Brcic, Joerg Lindenmann, Nicole Fink-Neuboeck, Franz Gollowitsch, Elvira Stacher-Priehse, Martin Asslaber, Margit Gogg-Kamerer, Jana Rolff, Jens Hoffmann, Alessandra Silvestri, Christian Regenbrecht, Christoph Reinhard, Anna-Maria Pehserl, Martin Pichler, Olga Sokolova, Michael Naumann, Valentin Mitterer, Brigitte Pertschy, Helmut Bergler, Helmut Popper, Wolfgang Sattler, Johannes Haybaeck.
      Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Dysregulation of protein synthesis plays a major role in carcinogenesis, a process regulated at multiple levels, including translation of mRNA into proteins. Ribosome assembly requires correct association of ribosome subunits, which is ensured by eukaryotic translation initiation factors (eIFs). eIFs have become targets in cancer therapy studies, and promising data on eIF6 in various cancer entities have been reported. Therefore, we hypothesised that eIF6 represents a crossroad for pulmonary carcinogenesis. High levels of eIF6 are associated with shorter patient overall survival in adenocarcinoma (ADC), but not in squamous cell carcinoma (SQC) of the lung. We demonstrate significantly higher protein expression of eIF6 in ADC and SQC than in healthy lung tissue based on immunohistochemical data from tissue microarrays (TMAs) and on fresh frozen lung tissue. Depletion of eIF6 in ADC and SQC lung cancer cell lines inhibited cell proliferation and induced apoptosis. Knockdown of eIF6 led to pre-rRNA processing and ribosomal 60S maturation defects. Our data indicate that eIF6 is upregulated in NSCLC, suggesting an important contribution of eIF6 to the development and progression of NSCLC and a potential for new treatment strategies against NSCLC.
    Keywords:  Adenocarcinoma; Eukaryotic translation initiation factor 6; Non–small cell lung cancer; Squamous cell carcinoma
    DOI:  https://doi.org/10.1016/j.ejca.2018.07.001
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