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10 pages, 18217 KiB

Open AccessArticle

Prognostic Significance of Glycolysis-Related Genes in Lung Squamous Cell Carcinoma

by Sultan F. Kadasah

Int. J. Mol. Sci. 2024, 25(2), 1143; https://doi.org/10.3390/ijms25021143 - 17 Jan 2024

Viewed by 1076

Abstract

Lung squamous cell carcinoma (LUSC) is one of the most common malignancies. There is growing evidence that glycolysis-related genes play a critical role in tumor development, maintenance, and therapeutic response by altering tumor metabolism and thereby influencing the tumor immune microenvironment. However, the overall impact of glycolysis-related genes on the prognostic significance, tumor microenvironment characteristics, and treatment outcome of patients with LUSC has not been fully elucidated. We used The Cancer Genome Atlas (TCGA) dataset to screen glycolysis-related genes with prognostic effects in LUSC and constructed signature and nomogram models using Lasso and Cox regression, respectively. In addition, we analyzed the immune infiltration and tumor mutation load of the genes in the models. We finally obtained a total of glycolysis-associated DEGs. The signature model and nomogram model had good prognostic power for LUSC. Gene expression in the models was highly correlated with multiple immune cells in LUSC. Through this analysis, we have identified and validated for the first time that glycolysis-related genes are highly associated with the development of LUSC. In addition, we constructed the signature model and nomogram model for clinical decision-making. Full article

(This article belongs to the Special Issue Recent Advances in Lung Cancer)

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25 pages, 6355 KiB

Open AccessArticle

Hypoxia Modulates Radiosensitivity and Response to Different Radiation Qualities in A549 Non-Small Cell Lung Cancer (NSCLC) Cells

by Hasan Nisar, Frederik M. Labonté, Marie Denise Roggan, Claudia Schmitz, François Chevalier, Bikash Konda, Sebastian Diegeler, Christa Baumstark-Khan and Christine E. Hellweg

Int. J. Mol. Sci. 2024, 25(2), 1010; https://doi.org/10.3390/ijms25021010 - 13 Jan 2024

Cited by 1 | Viewed by 1354

Abstract

Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations. This limited the possibility of simulating in vivo or clinical conditions in vitro. The presence of molecular oxygen is more important for the radiotoxicity of low-linear energy transfer (LET) radiation (e.g., X-rays) than that of high-LET carbon (¹²C) ions. The mechanisms responsible for ¹²C ions’ potential to overcome hypoxia-induced radioresistance are currently not fully understood. Therefore, the radioresistance of hypoxic A549 NSCLC cells following exposure to X-rays or ¹²C ions was investigated along with cell cycle progression and gene expression by maintaining hypoxia before, during and after irradiation. A549 cells were incubated under normoxia (20% O₂) or hypoxia (1% O₂) for 48 h and then irradiated with X-rays (200 kV) or ¹²C ions (35 MeV/n, LET ~75 keV/µm). Cell survival was evaluated using colony-forming ability (CFA) assays immediately or 24 h after irradiation (late plating). DNA double-strand breaks (DSBs) were analyzed using γH2AX immunofluorescence microscopy. Cell cycle progression was determined by flow cytometry of 4′,6-diamidino-2-phenylindole-stained cells. The global transcription profile post-irradiation was evaluated by RNA sequencing. When hypoxia was maintained before, during and after irradiation, hypoxia-induced radioresistance was observed only in late plating CFA experiments. The killing efficiency of ¹²C ions was much higher than that of X-rays. Cell survival under hypoxia was affected more strongly by the timepoint of plating in the case of X-rays compared to ¹²C ions. Cell cycle arrest following irradiation under hypoxia was less pronounced but more prolonged. DSB induction and resolution following irradiation were not significantly different under normoxia and hypoxia. Gene expression response to irradiation primarily comprised cell cycle regulation for both radiation qualities and oxygen conditions. Several PI3K target genes involved in cell migration and cell motility were differentially upregulated in hypoxic cells. Hypoxia-induced radioresistance may be linked to altered cell cycle response to irradiation and PI3K-mediated changes in cell motility and migration in A549 cells rather than less DNA damage or faster repair. Full article

(This article belongs to the Special Issue Recent Advances in Lung Cancer)

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Review

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20 pages, 400 KiB

Open AccessReview

Immune Checkpoint Inhibitors in “Special” NSCLC Populations: A Viable Approach?

by Giuseppe Bronte, Donato Michele Cosi, Chiara Magri, Antonio Frassoldati, Lucio Crinò and Luana Calabrò

Int. J. Mol. Sci. 2023, 24(16), 12622; https://doi.org/10.3390/ijms241612622 - 9 Aug 2023

Cited by 3 | Viewed by 1548

Abstract

Over the last decade, the therapeutic scenario for advanced non-small-cell lung cancer (NSCLC) has undergone a major paradigm shift. Immune checkpoint inhibitors (ICIs) have shown a meaningful clinical and survival improvement in different settings of the disease. However, the real benefit of this therapeutic approach remains controversial in selected NSCLC subsets, such as those of the elderly with active brain metastases or oncogene-addicted mutations. This is mainly due to the exclusion or underrepresentation of these patient subpopulations in most pivotal phase III studies; this precludes the generalization of ICI efficacy in this context. Moreover, no predictive biomarkers of ICI response exist that can help with patient selection for this therapeutic approach. Here, we critically summarize the current state of ICI efficacy in the most common “special” NSCLC subpopulations. Full article

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