Transmembrane p24 trafficking protein 2 regulates inflammation through the TLR4/NF-κB signaling pathway in lung adenocarcinoma DOI Creative Commons
Longhua Feng,

Pengjiang Cheng,

Zheng-yun Feng

et al.

World Journal of Surgical Oncology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Feb. 8, 2022

To investigate the role of transmembrane p24 trafficking protein 2 (TMED2) in lung adenocarcinoma (LUAD) and determine whether TMED2 knockdown could inhibit LUAD vitro vivo.TIMER2.0, Kaplan-Meier plotter, gene set enrichment analysis (GSEA), Target Gene, pan-cancer systems were used to predict potential function TMED2. Western blotting immunohistochemistry performed analyze expression different tissues or cell lines. The proliferation, development, apoptosis observed using a lentivirus-mediated knockdown. Bioinformatics western blot against inflammation via TLR4/NF-κB signaling pathway conducted.TMED2 tumor was higher than that normal positively correlated with poor survival cancer negatively LUAD. tumors HCC827 cells. inhibited development vivo increased levels inflammatory factors pathway. TME, immune score, TME-associated cells, their target markers, some mechanisms pathways, as determined TIMER2.0, GO, KEGG assays.TMED2 may regulate through enhance prognosis by regulating inflammation, which provide new strategy for treating inflammation.

Language: Английский

Metabolism-regulated ferroptosis in cancer progression and therapy DOI Creative Commons
Lvlan Ye,

Xiangqiong Wen,

Jiale Qin

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(3)

Published: March 8, 2024

Abstract Cancer metabolism mainly includes carbohydrate, amino acid and lipid metabolism, each of which can be reprogrammed. These processes interact with other to adapt the complicated microenvironment. Ferroptosis is a regulated cell death induced by iron-dependent peroxidation, morphologically different from apoptosis, necrosis, necroptosis, pyroptosis, autophagy-dependent cuprotosis. plays opposite roles in ferroptosis. On one hand, carbohydrate produce NADPH maintain GPX4 FSP1 function, provide substrates for synthesizing GPX4; on might synthesize PUFAs trigger The mechanisms through cancer affects ferroptosis have been investigated extensively long time; however, some not yet elucidated. In this review, we summarize interaction between Importantly, were most concerned how these targets utilized therapy.

Language: Английский

Citations

25
Ferroptosis in Non-Small Cell Lung Cancer: Progression and Therapeutic Potential on It DOI Open Access

Jiayu Zou,

Li Wang, Hailin Tang

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(24), P. 13335 - 13335

Published: Dec. 11, 2021

As a main subtype of lung cancer, the current situation non-small cell cancer (NSCLC) remains severe worldwide with 19% survival rate at 5 years. conventional therapy approaches, such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy, gradually develop into resistance, searching for novel therapeutic strategy NSCLC is urgent. Ferroptosis, an iron-dependent programmed necrosis, has now been widely considered key factor affecting tumorigenesis progression in various cancers. Focusing on its effect NSCLC, different situations, ferroptosis can be triggered or restrained. When was induced it available to inhibit tumor both vitro vivo. The dominating mechanism due regulation classic ferroptosis-repressed GSH-dependent GPX4 signaling pathway instead other fractional regulating signal axes that regulated via impacting ROS, cellular iron levels, etc. In terms prevention GSH-independent also discovered, interestingly exhibiting same upstream signaling. addition, this review summarizes elaborates their association specific mechanisms through bioinformatics analysis multiple experimental evidence from cascades. Finally, points out possibility working resistance emphasizing potential.

Language: Английский

Citations

80
The interplay of oncogenic signaling, oxidative stress and ferroptosis in cancer DOI
Wentao Zeng,

Xiaohang Long,

Pu‐Ste Liu

et al.

International Journal of Cancer, Journal Year: 2023, Volume and Issue: 153(5), P. 918 - 931

Published: Feb. 27, 2023

Abstract Oncogene‐induced hyper‐proliferation in cancer cells is accompanied by the onset of different stresses, including DNA‐replication stress, metabolic stress and oxidative stress. Excessive accumulation reactive oxygen species (ROS) plays a pivotal contradictory role tumor progression. ROS dictates multitude cell signaling pathways to facilitate malignant transformation cells. In meantime, burden mandates reinforcing antioxidant capacity mitigate detrimental damages. The addiction increased iron demands also impinges on sensitivity ferroptosis. Targeting redox homeostasis ferroptosis overcome drug resistance treatment has become an attractive research topic. However, roles oncogenic regulation have not been comprehensively discussed. this review, we summarize current knowledge regarding interplay between context biology. We emphasize implication regulation. provide overview strategies targeting treatment.

Language: Английский

Citations

37
Molecular subtypes of lung adenocarcinoma patients for prognosis and therapeutic response prediction with machine learning on 13 programmed cell death patterns DOI
Qin Wei, Xiaoyu Jiang, Xinyi Miao

et al.

Journal of Cancer Research and Clinical Oncology, Journal Year: 2023, Volume and Issue: 149(13), P. 11351 - 11368

Published: June 28, 2023

Language: Английский

Citations

28
A Prognostic Risk Score Based on Hypoxia-, Immunity-, and Epithelialto-Mesenchymal Transition-Related Genes for the Prognosis and Immunotherapy Response of Lung Adenocarcinoma DOI Creative Commons
Wenhao Ouyang, Yupeng Jiang,

Shiyi Bu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 9

Published: Jan. 24, 2022

Background: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer (NSCLC), is associated with poor prognosis. However, current stage-based clinical methods are insufficient for survival prediction and decision-making. This study aimed to establish a novel model evaluating risk LUAD based on hypoxia, immunity, epithelial-mesenchymal transition (EMT) gene signatures. Methods: In this study, we used data from TCGA-LUAD training cohort GSE68465 GSE72094 validation cohorts. Immunotherapy datasets GSE135222, GSE126044, IMvigor210 were obtained previous study. Using bioinformatic machine algorithms, established immune, EMT signatures, which was then divide patients into high low groups. We analyzed differences in enriched pathways between two groups, following investigated whether score correlated stemness scores, genes related m6A, m5C, m1A m7G modification, immune microenvironment, immunotherapy response, multiple anti-cancer drug sensitivity. Results: Overall differed significantly high-risk low-risk groups (HR = 4.26). The AUCs predicting 1-, 3-, 5-year 0.763, 0.766, 0.728, respectively. dataset, HR 2.03, while 0.69, 0.651, 0.618, corresponding values dataset an 2.36 0.653, 0.662, 0.749, could independently predict OS LUAD, highly scores numerous modification-related genes. Furthermore, microenvironment characteristics. GSE135222 4.26 AUC 0.702. Evaluation GSE126044 cohorts indicated that PD-1/PD-LI inhibitor treatment may be therapy various drugs scores. Conclusion: Our developed signatures can aid prognosis guiding LUAD.

Language: Английский

Citations

34
Immune, metabolic landscapes of prognostic signatures for lung adenocarcinoma based on a novel deep learning framework DOI Creative Commons

Shimei Qin,

Shibin Sun, Yahui Wang

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Jan. 4, 2024

Abstract Lung adenocarcinoma (LUAD) is a malignant tumor with high lethality, and the aim of this study was to identify promising biomarkers for LUAD. Using TCGA-LUAD dataset as discovery cohort, novel joint framework VAEjMLP based on variational autoencoder (VAE) multilayer perceptron (MLP) proposed. And Shapley Additive Explanations (SHAP) method introduced evaluate contribution feature genes classification decision, which helped us develop biologically meaningful biomarker potential scoring algorithm. Nineteen LUAD were identified, involved in regulation immune metabolic functions A prognostic risk model constructed by HLA-DRB1, SCGB1A1, HLA-DRB5 screened Cox regression analysis, dividing patients into high-risk low-risk groups. The validated external datasets. group characterized enrichment pathways higher infiltration compared group. While, accompanied an increase pathway activity. There significant differences between high- groups reprogramming aerobic glycolysis, amino acids, lipids, well angiogenic activity, epithelial-mesenchymal transition, tumorigenic cytokines, inflammatory response. Furthermore, more sensitive Afatinib, Gefitinib, Gemcitabine predicted pRRophetic This provides signatures capable revealing landscapes LUAD, may shed light identification other cancer biomarkers.

Language: Английский

Citations

6
Ferroptosis in age-related vascular diseases: Molecular mechanisms and innovative therapeutic strategies DOI Open Access
Yue Dai, Xiuxian Wei, Tao Jiang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 173, P. 116356 - 116356

Published: Feb. 29, 2024

Aging, an inevitable aspect of human existence, serves as one the predominant risk factors for vascular diseases. Delving into mystery disease's pathophysiology, profound involvement programmed cell death (PCD) has been extensively demonstrated. PCD is a fundamental biological process that plays crucial role in both normal physiology and pathology, including recently discovered form, ferroptosis. Ferroptosis characterized by its reliance on iron lipid peroxidation, significant disease pathophysiology increasingly acknowledged. This phenomenon not only offers promising therapeutic target but also deepens our understanding complex relationship between ferroptosis age-related Consequently, this article aims to thoroughly review mechanisms enable effective control inhibition It focuses genetic pharmacological interventions, with goal developing innovative strategies combat

Language: Английский

Citations

6
Prognostic Ferroptosis-Related lncRNA Signatures Associated With Immunotherapy and Chemotherapy Responses in Patients With Stomach Cancer DOI Creative Commons

Donglin Lai,

Lin Tan, Xiaojia Zuo

et al.

Frontiers in Genetics, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 3, 2022

Ferroptosis is associated with the prognosis and therapeutic responses of patients various cancers. LncRNAs are reported to exhibit antitumor or oncogenic functions. Currently, few studies have assessed combined effects ferroptosis lncRNAs on therapy stomach cancer. In this study, transcriptomic clinical data were downloaded from TCGA database, ferroptosis-related genes obtained FerrDb database. Through correlation analysis, Cox Lasso algorithm, 10 prognostic (AC009299.2, AC012020.1, AC092723.2, AC093642.1, AC243829.4, AL121748.1, FLNB-AS1, LINC01614, LINC02485, LINC02728) screened construct a model, which was verified in two test cohorts. Risk scores for cancer calculated, divided into risk groups. The low-risk group, based median value, had longer overall survival time KM curve, lower proportion dead distribution curve. Potential mechanisms possible functions revealed using GSEA ceRNA network. By integrating information, association between features analyzed several affecting identified. Then, nomogram developed predict rates, its good predictive performance indicated by relatively high C-index (0.67118161) match calibration curves. Next, these explored. Patients group an immune-activating environment, higher immune scores, TMB, TIDE expression checkpoints, suggesting they might receive greater benefit checkpoint inhibitor therapy. addition, significant difference sensitivity mitomycin. C, cisplatin, docetaxel, but not etoposide paclitaxel, observed. summary, model guiding significance personalized It helped screen who immunotherapy guided selection chemotherapeutic drugs.

Language: Английский

Citations

27
Machine Learning-Based Integration Develops a Macrophage-Related Index for Predicting Prognosis and Immunotherapy Response in Lung Adenocarcinoma DOI
Zuwei Li, Minzhang Guo, Wanli Lin

et al.

Archives of Medical Research, Journal Year: 2023, Volume and Issue: 54(7), P. 102897 - 102897

Published: Oct. 19, 2023

Language: Английский

Citations

14
Ferroptosis: Molecular perspective, cellular influence, cancer manifestation, and therapeutic potentials DOI
Pawan Kumar Pandey,

Saurabh Bhorkade,

Shikha Jha

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 100, P. 105998 - 105998

Published: July 31, 2024

Language: Английский

Citations

5