Proteomics of adjacent-to-tumor samples uncovers clinically relevant biological events in hepatocellular carcinoma DOI Creative Commons
Hongwen Zhu, Youpei Lin,

Dayun Lu

et al.

National Science Review, Journal Year: 2023, Volume and Issue: 10(8)

Published: June 2, 2023

ABSTRACT Normal adjacent tissues (NATs) of hepatocellular carcinoma (HCC) differ from healthy liver and their heterogeneity may contain biological information associated with disease occurrence clinical outcome that has yet to be fully evaluated at the proteomic level. This study provides a detailed description NATs differences between livers revealed molecular features tumor subgroups in HCC were partially reflected respective NATs. Proteomic data classified into two subtypes (Subtypes 1 2), Subtype 2 was poor prognosis high-risk recurrence. The pathway immune these characterized. NAT further investigated using data-independent acquisition mass spectrometry, revealing early alterations progression high-quality resource for researchers clinicians significantly expand knowledge eventually benefit practice.

Language: Английский

The inflammatory pathogenesis of colorectal cancer DOI
Mark R. Schmitt, Florian R. Greten

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(10), P. 653 - 667

Published: April 28, 2021

Language: Английский

Citations

499
Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma DOI Creative Commons
Liangqing Dong,

Dayun Lu,

Ran Chen

et al.

Cancer Cell, Journal Year: 2021, Volume and Issue: 40(1), P. 70 - 87.e15

Published: Dec. 30, 2021

Language: Английский

Citations

230
Cancer proteogenomics: current impact and future prospects DOI
D.R. Mani, Karsten Krug, Bing Zhang

et al.

Nature reviews. Cancer, Journal Year: 2022, Volume and Issue: 22(5), P. 298 - 313

Published: March 2, 2022

Language: Английский

Citations

150
The updated role of exosomal proteins in the diagnosis, prognosis, and treatment of cancer DOI Creative Commons
Xinyi Wang, Jing Huang, Wenjie Chen

et al.

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: unknown

Published: Sept. 22, 2022

Abstract Exosomes are vesicles encompassed by a lipid bilayer that released various living cells. Exosomal proteins encapsulated within the membrane or embedded on surface. As an important type of exosome cargo, exosomal can reflect physiological status parent cell and play essential role in cell–cell communication. regulate tumor development, including tumor-related immune regulation, microenvironment reconstruction, angiogenesis, epithelial–mesenchymal transition, metastasis, etc. The features provide insight into generation, targeting, biological function potential sources markers for cancer diagnosis, prognosis, treatment. Here, we summarize effects biology, latest progress application diagnosis contribution therapeutics vaccines.

Language: Английский

Citations

128
Multi-omics approaches for biomarker discovery in early ovarian cancer diagnosis DOI Creative Commons
Yinan Xiao,

Meiyu Bi,

Hongyan Guo

et al.

EBioMedicine, Journal Year: 2022, Volume and Issue: 79, P. 104001 - 104001

Published: April 16, 2022

Ovarian cancer (OC) is a heterogeneous disease with the highest mortality rate and poorest prognosis among gynecological malignancies. Because of absence specific early symptoms, most OC patients are often diagnosed at late stages. Thus, improved biomarkers for use in research clinical practice urgently needed. The last decade has seen increasingly rapid advances sequencing biotechnological methodologies. Consequently, multiple omics technologies, including genomic/transcriptomic sequencings proteomic/metabolomic mass spectra, have been widely applied to analyze tissue- liquid-derived samples from patients. integration multi-omics data increased our knowledge identified valuable biomarkers. In this review, we summarize recent perspectives technologies highlight potential applications identifying novel improving assessments.

Language: Английский

Citations

127
Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications DOI Creative Commons
Qian Zhong,

Xina Xiao,

Yijie Qiu

et al.

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Language: Английский

Citations

124
A proteogenomic analysis of clear cell renal cell carcinoma in a Chinese population DOI Creative Commons
Yuanyuan Qu, Jinwen Feng, Xiaohui Wu

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 19, 2022

Abstract Clear cell renal carcinoma (ccRCC) is a common and aggressive subtype of cancer. Here we conduct comprehensive proteogenomic analysis 232 tumor adjacent non-tumor tissue pairs from Chinese ccRCC patients. By comparing with tissues, find that shows extensive metabolic dysregulation an enhanced immune response. Molecular subtyping classifies tumors into three subtypes (GP1–3), among which the most GP1 exhibits strongest phenotype, increased metastasis, imbalance, linking multi-omics-derived phenotypes to clinical outcomes ccRCC. Nicotinamide N-methyltransferase (NNMT), one-carbon enzyme, identified as potential marker drug target for GP1. We demonstrate NNMT induces DNA-dependent protein kinase catalytic subunit (DNA-PKcs) homocysteinylation, increases DNA repair, promotes growth. This study provides insights biological underpinnings prognosis assessment ccRCC, revealing targetable vulnerabilities.

Language: Английский

Citations

90
Benchmarking commonly used software suites and analysis workflows for DIA proteomics and phosphoproteomics DOI Creative Commons
Ronghui Lou, Ye Cao, Shanshan Li

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 6, 2023

A plethora of software suites and multiple classes spectral libraries have been developed to enhance the depth robustness data-independent acquisition (DIA) data processing. However, how combination a DIA tool library impacts outcome proteomics phosphoproteomics analysis has rarely investigated using benchmark that mimics biological complexity. In this study, we create sets simulating regulation thousands proteins in complex background, which are collected on both an Orbitrap timsTOF instruments. We evaluate four commonly used (DIA-NN, Spectronaut, MaxDIA Skyline) combined with seven different global proteome analysis. Moreover, assess their performances analyzing phosphopeptide standards TNF-α-induced phosphoproteome regulation. Our study provides practical guidance construct robust pipeline for studies implementing technique.

Language: Английский

Citations

74
Macrophage STING signaling promotes NK cell to suppress colorectal cancer liver metastasis via 4-1BBL/4-1BB co-stimulation DOI Creative Commons
Yu Sun,

Haoran Hu,

Zheng Liu

et al.

Journal for ImmunoTherapy of Cancer, Journal Year: 2023, Volume and Issue: 11(3), P. e006481 - e006481

Published: March 1, 2023

Background and aims Macrophage innate immune response plays an important role in tumorigenesis. However, the mechanism of macrophage STING signaling modulating tumor microenvironment to suppress growth at secondary sites remains largely unclear. Methods expression was assessed liver samples from patients with colorectal cancer (CRC) metastasis. Global or myeloid stimulator interferon gene (STING)-deficient mice, NOD-like receptor protein 3 (NLRP3)-deficient wild-type (WT) mice were subjected a mouse model CRC metastasis by intrasplenic injection murine colon carcinoma cells (MC38). Liver non-parenchymal including macrophages natural killer (NK) isolated for flow cytometry analysis. Bone marrow-derived pretreated MC38 co-cultured splenic NK vitro studies. Results Significant activation detected adjacent tissues intrahepatic macrophages. STING-deficient had exacerbated shorten survival, decreased infiltration impaired antitumor function cells. Depletion WT animals increased their metastatic burden, while no significant effects observed mice. contributed secretion interleukin (IL)-18 IL-1β macrophages, which optimized activity promoting 4-1BBL 4-1BB cells, respectively. Moreover, treatment activated NLRP3 signaling, inhibited depletion. Myeloid deficiency burden suppressed its agonist effectively SITNG-deficient Conclusions We demonstrated that promoted NLRP3-mediated IL-18 production optimize via co-stimulation 4-1BBL/4-1BB.

Language: Английский

Citations

56
5‐hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target DOI Creative Commons
Nuo Xu, Zhaoya Gao, Deyan Wu

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(2)

Published: Feb. 1, 2025

Abstract Metachronous liver metastases (MLM) are characterised by high incidence and mortality in clinical colorectal cancer treatment. Currently traditional methods cannot effectively predict prevent the occurrence of metachronous metastasis cancer. Based on 5hmC‐Seal analysis blood tissue samples, this study found that portal venous was more relevant to tumour gDNA than peripheral blood. We performed a novel epigenetic liquid biopsy strategy using 10 5hmC alterations, accurately distinguish MLM patients from without metastases. Among these phosphodiesterase 4 (PDE4D) highly increased correlated with poor survival. Moreover, our studies demonstrated PDE4D key metastasis‐driven target for drug development. Interfering function significantly repressed Similarly, roflumilast, PDE4 inhibitor chronic obstructive pulmonary disease (COPD) therapy, also inhibits Further indicate blocking can affect CRC invasion through HIF‐1α‐CCN2 pathway. To develop efficient reduce adverse events, we designed several new compounds based 2‐arylbenzofurans discovered lead L11 potent affinity significant suppression In work, provides promising predicting discovers as potential repurposed inhibiting metastasis, which have benefit future. Key points markers derived could promoted via The newly synthesised compound specifically inhibit abolish obvious toxic side effects.

Language: Английский

Citations

2