bims-meluca 2021-11-14 papers

Front Oncol. 2021 ;11 757323

Alternative Energy: Breaking Down the Diverse Metabolic Features of Lung Cancers.

Kasey R Cargill, William L Hasken, Carl M Gay, Lauren A Byers.

Metabolic reprogramming is a hallmark of cancer initiation, progression, and relapse. From the initial observation that cancer cells preferentially ferment glucose to lactate, termed the Warburg effect, to emerging evidence indicating that metabolic heterogeneity and mitochondrial metabolism are also important for tumor growth, the complex mechanisms driving cancer metabolism remain vastly unknown. These unique shifts in metabolism must be further investigated in order to identify unique therapeutic targets for individuals afflicted by this aggressive disease. Although novel therapies have been developed to target metabolic vulnerabilities in a variety of cancer models, only limited efficacy has been achieved. In particular, lung cancer metabolism has remained relatively understudied and underutilized for the advancement of therapeutic strategies, however recent evidence suggests that lung cancers have unique metabolic preferences of their own. This review aims to provide an overview of essential metabolic mechanisms and potential therapeutic agents in order to increase evidence of targeted metabolic inhibition for the treatment of lung cancer, where novel therapeutics are desperately needed.

Keywords: glycolysis (Warburg effect); lung cancer; metabolic inhibitors; metabolism; oxidative phosphorylation

DOI: https://doi.org/10.3389/fonc.2021.757323

J Clin Lab Anal. 2021 Nov 09. e24086

Dysregulated ferroptosis-related genes indicate potential clinical benefits for anti-PD-1/PD-L1 immunotherapy in lung adenocarcinoma.

Min Zhou, Xiuxiu Zhang, Tianyang Li, Yan Chen.

BACKGROUND: Ferroptosis is an iron-dependent programmed cell death mechanism that influences the development of malignancy. Lung adenocarcinoma (LUAD) is the most common type of lung cancer with no known cure. Anti-PD-1/PD-L immunotherapy is effective for patients with partial LUAD. Therefore, there is an immediate requirement of novel markers to predict the individualised benefits of immunotherapy.
METHODS: We manually collected the ferroptosis-related gene (FERG) set and employed the Wilcoxon rank-sum test to identify the differentially expressed FERGs. Subsequently, we constructed a recursive partitioning and regression tree (RPART) model to predict the benefits of anti-PD-1/PD-L1 immunotherapy. Subsequently, the ROC curve and AUC were used to evaluate the model efficiency in an independent dataset.
RESULTS: In this study, we found that the dysregulated FERGs were closely associated with multiple metabolic processes in LUAD. Furthermore, we identified three ferroptosis-related tumour subtypes (F1, F3 and F3). The F3 subtype exhibited higher immunoactivity and lower tumour purity, mutation count and aneuploidy and had better survival outcomes compared with the other two subtypes, implying that FERGs played an important role in intertumoral immune heterogeneity. We further explored the role of FERGs in the anti-PD-1/PD-L1 immunotherapy. We identified a set of three-FERGs signature (CD44, G6PD and ZEB1) that acted as a promising indicator (AUC = 0.697) for the prediction of the benefits of anti-PD-1/PD-L1 immunotherapy.
CONCLUSION: Ferroptosis, as emerging programmed cell death mechanism, was associated with cancer development. We used ferroptosis-related genes to predict the immunotherapy benefits that may facilitate the development of individualised anti-cancer treatment strategies.

Keywords: anti-PD-1/PD-L1 immunotherapy; decision model; ferroptosis; immune heterogeneity; lung adenocarcinoma

DOI: https://doi.org/10.1002/jcla.24086

Int J Biol Markers. 2021 Nov 11. 17246008211052571

The isocitrate dehydrogenase 1 is a potential prognostic indicator for non-small cell lung cancer patients.

Xintong Zhang, Shang Ma, Yan Chen, Yanjun Yin, Wanqiu Bai, Jinjing Tan, Guangli Shi.

BACKGROUND: The serum isocitrate dehydrogenase 1(IDH1) level is significantly elevated in patients with non-small cell lung cancer (NSCLC) and has important clinical value as a marker for early diagnosis. This study examined the dynamic changes of serum IDH1 levels of patients with NSCLC undergoing surgery or medical treatment, to evaluate its potential prognostic value.
METHODS: The study cohort included 83 NSCLC patients who underwent surgery, 37 NSCLC patients who underwent medical treatment, 50 healthy controls, and 52 disease controls. Serum levels of IDH1 were assayed by enzyme-linked immunoassay. Tumor biomarkers including carcinoembryonic antigen, squamous cell carcinoma, neuron-specific enolase, CYFRA21-1, and pro-gastrin-releasing peptide-which are currently used in clinical practice-were measured by automatic immunoanalyzers.
RESULTS: Serum IDH1 was significantly higher in patients with NSCLC compared with healthy people or patients with benign lung diseases (p < 0.001). The area under the receiver operating characteristic curve for diagnosis and differential diagnosis were 0.897 and 0.879, respectively, which were superior to the five tumor markers. Serum IDH1 levels decreased in most patients after surgery, with the most dramatic changes in patients with stage I tumors compared with stage II and III. Analyses of changes in the serum IDH1 level of patients after receiving chemotherapy or targeted therapy revealed that for patients with progressive disease, serum IDH1 increased significantly after treatment; for patients with partial response or stable disease, it decreased steadily.
CONCLUSION: IDH1 has potential prognostic value and may be used as a marker for the monitoring of treatment efficacy.

Keywords: IDH1; NSCLC; chemotherapy; prognosis; serum biomarkers

DOI: https://doi.org/10.1177/17246008211052571