Proteogenomic characterization of 2002 human cancers reveals pan-cancer molecular subtypes and associated pathways

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Май 13, 2022

Abstract Mass-spectrometry-based proteomic data on human tumors—combined with corresponding multi-omics data—present opportunities for systematic and pan-cancer proteogenomic analyses. Here, we assemble a compendium dataset of proteomics 2002 primary tumors from 14 cancer types 17 studies. Protein expression genes broadly correlates mRNA levels or copy number alterations (CNAs) across tumors, but notable exceptions. Based unsupervised clustering, separate into 11 distinct proteome-based subtypes spanning multiple tissue-based types. Two are enriched brain one subtype associating MYC, Wnt, Hippo pathways high CNA burden, another metabolic low burden. Somatic alteration in pathway associates higher activity as inferred by proteome transcriptome data. A substantial fraction cancers shows MYC without gain mutations noncanonical roles MYC. Our proteogenomics survey reveals the interplay between genome tumor lineages.

Язык: Английский

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Targeting CDK1 in cancer: mechanisms and implications

npj Precision Oncology, Год журнала: 2023, Номер 7(1)

Опубликована: Июнь 13, 2023

Abstract Cyclin dependent kinases (CDKs) are serine/threonine that proposed as promising candidate targets for cancer treatment. These proteins complexed with cyclins play a critical role in cell cycle progression. Most CDKs demonstrate substantially higher expression tissues compared normal and, according to the TCGA database, correlate survival rate multiple types. Deregulation of CDK1 has been shown be closely associated tumorigenesis. activation plays wide range types; and phosphorylation its many substrates greatly influences their function Enrichment interacting Kyoto Encyclopedia Genes Genomes (KEGG) pathway analysis was conducted participate oncogenic pathways. This abundance evidence clearly supports target therapy. A number small molecules targeting or have developed evaluated preclinical studies. Notably, some these also subjected human clinical trials. review evaluates mechanisms implications tumorigenesis

Язык: Английский

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Comprehensive pan-cancer analysis reveals ENC1 as a promising prognostic biomarker for tumor microenvironment and therapeutic responses

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 25, 2024

Accumulating research showed that ENC1 plays a critical role in maintaining the physiological functions. However, little is known about its predicting prognosis and immunotherapy response across cancers. In our results, compared to normal tissues, most cancer tissues exhibit increased expression. We found common type of genetic variation was gene mutation. addition, positive correlation between CNV Moreover, overexpression positively correlated with poor clinical outcomes. The GSEA results closely tumor-promoting biological functions also negatively associated infiltration levels T cells, activated NK B cells. Most immunomodulators are ENC1. Further, we verified inhibition expression suppressed proliferation migration breast cancer, pancreatic glioma conclusion, study demonstrated protumorigenic Additionally, tumor microenvironment features immune checkpoint inhibitors Overall, could serve as promising potential prognostic biomarker various tumors.

Язык: Английский

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FDX1 downregulation activates mitophagy and the PI3K/AKT signaling pathway to promote hepatocellular carcinoma progression by inducing ROS production

Redox Biology, Год журнала: 2024, Номер 75, С. 103302 - 103302

Опубликована: Авг. 6, 2024

Mitochondrial dysfunction and metabolic reprogramming can lead to the development progression of hepatocellular carcinoma (HCC). Ferredoxin 1 (FDX1) is a small mitochondrial protein recent studies have shown that FDX1 plays an important role in tumor cuproptosis, but its HCC still elusive. In this study, we aim investigate expression novel functions HCC.

Язык: Английский

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Acidosis activates breast cancer ferroptosis through ZFAND5/SLC3A2 signaling axis and elicits M1 macrophage polarization

Cancer Letters, Год журнала: 2024, Номер 587, С. 216732 - 216732

Опубликована: Фев. 14, 2024

Язык: Английский

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The Role of PLIN3 in Prognosis and Tumor-Associated Macrophage Infiltration: A Pan-Cancer Analysis

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 3757 - 3777

Опубликована: Март 1, 2025

Nucleolar and spindle-associated protein 1 (PLIN3), a member of the perilipin family, plays critical role in lipid droplet dynamics is implicated promoting tumor progression across several cancers. However, its influence on immune microenvironment potential as prognostic indicator regarding immunotherapy responses have yet to be systematically evaluated. This study leverages data retrieved from multiple databases address these questions. PLIN3 mRNA expressions were analyzed diverse range normal cancerous tissues, utilizing databases. The diagnostic biomarker cancers was assessed. Advanced computational algorithms employed examine impact cell infiltration. association between expression presence M2 macrophages validated through analyses incorporating bulk single-cell transcriptomics, spatial multicolor fluorescence staining techniques. Furthermore, effects malignancy growth investigated vitro lung adenocarcinoma (LUAD) cells. Potential compounds targeting identified using Connectivity Map (cMap) web tool, their efficacy further assessed molecular docking. predominantly upregulated various cancers, correlating with adverse outcomes. A strong positive observed levels macrophage infiltration cancer types, establishing it pan-cancer marker for presence. confirmed by integrative multi-omics analysis staining. Additionally, knockdown LUAD cells diminished malignant traits, resulting decreased proliferation migration. In LUAD, clofibrate inhibitor PLIN3's pro-oncogenic functions. may serve oncogene, particularly LUAD. It key mediating presents promising immunotherapeutic target.

Язык: Английский

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Comprehensive pan-cancer analysis reveals NTN1 as an immune infiltrate risk factor and its potential prognostic value in SKCM

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 25, 2025

Netrin-1 (NTN1) is a laminin-related secreted protein involved in axon guidance and cell migration. Previous research has established significant connection between NTN1 nervous system development. In recent years, mounting evidence indicates that also plays crucial role tumorigenesis tumor progression. For instance, inhibiting been shown to suppress growth epithelial-mesenchymal transition (EMT) characteristics endometrial cancer. To further elucidate the influence of genes on tumors, we utilized variety machine learning techniques found strongly linked multiple cancer types, suggesting it as potential therapeutic target. This study aimed pan-cancer using multi-omics data explore its prognostic biomarker SKCM. Analysis TCGA, GTEx, UALCAN databases revealed differences expression at both mRNA levels. Prognostic value was evaluated through univariate Cox regression Kaplan–Meier methods. Mutation methylation analyses were conducted cBioPortal SMART databases. We identified interacting with correlated STRING GEPIA2, respectively. Subsequently, performed GO KEGG enrichment analyses. The results suggested might be biological processes pathways related development progression, including adhesion, guidance, immune response, various signaling pathways. then explored correlation infiltration well immunotherapy ESTIMATE package, TIMER2.0, TISIDB, TIDE, TIMSO, TCIA. relationship heterogeneity, stemness, DNA methyltransferases, MMR examined. Lastly, constructed nomogram based SKCM investigated association drug sensitivity. significantly associated infiltration, molecular subtypes, clinicopathological features cancers. Genetic analysis Deep deletions most common type alteration. Additionally, positive observed CNAs cancers, showed correlations stromal scores, specific populations. Its predictive for response comparable mutational burden. Furthermore, exhibited methyltransferase genes, genes. SKCM, an independent risk factor demonstrated associations drugs. exhibits substantial clinical utility marker indicator across types. comprehensive provides insights into implications research.

Язык: Английский

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VSTM2L protects prostate cancer cells against ferroptosis via inhibiting VDAC1 oligomerization and maintaining mitochondria homeostasis

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 29, 2025

Ferroptosis is a form of iron-dependent programmed cell death, which distinct from apoptosis, necrosis, and autophagy. Mitochondria play critical role in initiating amplifying ferroptosis cancer cells. Voltage-Dependent Anion Channel 1 (VDAC1) embedded the mitochondrial outer membrane, exerts roles regulation ferroptosis. However, mechanisms VDAC1 oligomerization regulating are not well elucidated. Here, we identify that binding protein V-Set Transmembrane Domain Containing 2 Like (VSTM2L), mainly localized to mitochondria, positively associated with prostate (PCa) progression, key regulator Moreover, VSTM2L knockdown PCa cells enhances sensitivity RSL3-induced Mechanistically, forms complex hexokinase (HK2), enhancing their affinity preventing oligomerization, thereby inhibiting maintaining mitochondria homeostasis vitro vivo. Collectively, our findings reveal pivotal for mitochondria-localized driving resistance highlight its potential as ferroptosis-inducing therapeutic target treatment PCa.

Язык: Английский

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IGF2BP3 is an essential N6-methyladenosine biotarget for suppressing ferroptosis in lung adenocarcinoma cells

Materials Today Bio, Год журнала: 2022, Номер 17, С. 100503 - 100503

Опубликована: Ноя. 24, 2022

A lack of promising targets leads to poor prognosis in patients with lung adenocarcinoma (LUAD). Therefore, it is urgent identify novel therapeutic targets. The importance the N6-methyladenosine (m6A) RNA modification has been demonstrated various types tumors; however, knowledge m6A-related proteins LUAD still limited. Here, we found that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), an m6A reader protein, highly expressed and associated prognosis. IGF2BP3 desensitizes ferroptosis (a new form regulated cell death) a manner dependent on its reading domain capacity m6A-methylated mRNAs encoding anti-ferroptotic factors, including but not limited glutathione peroxidase 4 (GPX4), solute carrier family member (SLC3A2), acyl-CoA synthetase long chain (ACSL3), ferritin heavy 1 (FTH1). After overexpression, expression levels stabilities these factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, revealed clinical specimens, further establishing essential role desensitizing ferroptosis. Inducing gradually accepted as alternative strategy treat tumors. Thus, could be potential target for future development biomaterial-associated anti-tumor drugs.

Язык: Английский

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Comprehensive analysis of the potential cuproptosis-related biomarker LIAS that regulates prognosis and immunotherapy of pan-cancers

Frontiers in Oncology, Год журнала: 2022, Номер 12

Опубликована: Авг. 2, 2022

Lipoic acid synthetase (LIAS) has been demonstrated to play a crucial role in the progression of cancer. Exploring underlying mechanisms and biological functions LIAS could have potential therapeutic guidance for cancer treatment. Our study explored expression levels prognostic values pan-cancer through several bioinformatics platforms, including TIMER2.0, Gene Expression Profiling Interactive Analysis, version 2 (GEPIA2.0), Human Protein Atlas (HPA). We found that high was related good prognosis patients with kidney renal clear cell carcinoma (KIRC), rectum adenocarcinoma (READ), breast cancer, ovarian Inversely, showed unfavorable lung patients. In addition, genetic alteration, methylation levels, immune analysis evaluated. To elucidate molecular mechanism LIAS, we conduct single-cell sequencing implicate hypoxia, angiogenesis, DNA repair. Thus, these comprehensive analyses conveyed be potentially significant various cancers. Moreover, predict efficacy immunotherapy

Язык: Английский

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