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

Integrative proteogenomic characterization of early esophageal cancer DOI Creative Commons
Lingling Li, Dongxian Jiang, Qiao Zhang

et al.

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

Published: March 25, 2023

Abstract Esophageal squamous cell carcinoma (ESCC) is malignant while the carcinogenesis still unclear. Here, we perform a comprehensive multi-omics analysis of 786 trace-tumor-samples from 154 ESCC patients, covering 9 histopathological stages and 3 phases. Proteogenomics elucidates cancer-driving waves in progression, reveals molecular characterization alcohol drinking habit associated signatures. We discover chromosome 3q gain functions transmit nontumor to intraepithelial neoplasia phases, find TP53 mutation enhances DNA replication phase. The mutations AKAP9 MCAF1 upregulate glycolysis Wnt signaling, respectively, advanced-stage Six major tracks related different clinical features during progression are identified, which validated by an independent cohort with another 256 samples. Hyperphosphorylated phosphoglycerate kinase 1 (PGK1, S203) considered as drug target progression. This study provides insight into understanding mechanism development therapeutic targets.

Language: Английский

Citations

35
Molecular Profiling Provides Clinical Insights Into Targeted and Immunotherapies as Well as Colorectal Cancer Prognosis DOI Creative Commons

Linwei Guo,

Yunjin Wang,

Wenxiao Yang

et al.

Gastroenterology, Journal Year: 2023, Volume and Issue: 165(2), P. 414 - 428.e7

Published: May 3, 2023

Tumor genetic testing is indispensable in the management of primary and metastatic colorectal cancer (CRC), yet indications for genomics-guided precision medicine immunotherapy must be better understood defined.We prospectively sequenced tumors from 869 Chinese patients with CRC by a large panel evaluated clinical significance single-gene somatic mutations co-occurring events CRC, as well their functional effects tumorigenic mechanisms. We systematically assessed heterogeneity tumor immune microenvironment different genomic contexts through combined analysis Immunoscore, multiplex immunostaining, whole-exome sequencing, transcriptome, single-cell sequencing.Single-gene BRAF or RBM10 were associated shorter progression-free survival CRC. Functional studies suggested acts suppressor development. Co-mutations KRAS/AMER1 KRAS/APC enriched cohort, which had poor did not benefit bevacizumab due to accelerated drug metabolism. Forty (4.6%) carried pathogenic likely germline alterations DNA damage repair pathway 37.5% these secondary-hit loss heterozygosity biallelic alterations. A high insertion deletion burden microsatellite instability immunogenicity numerous activated tumor-infiltrating lymphocytes, whereas polymerase epsilon exonuclease mutation ultrahigh indicated relatively quiescent immunophenotype. The heterogeneous genomic-immunologic interactions reflected divergent neoantigen presentation depletion, checkpoint expression, PD-1/PD-L1 interaction, T-cell responsiveness pembrolizumab.Our integrated provides insights into prognostic stratification, response, personalized targeted immunotherapies.

Language: Английский

Citations

32
Multilevel proteomic analyses reveal molecular diversity between diffuse-type and intestinal-type gastric cancer DOI Creative Commons
Wenhao Shi, Yushen Wang, Chen Xu

et al.

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

Published: Feb. 14, 2023

Abstract Diffuse-type gastric cancer (DGC) and intestinal-type (IGC) are the major histological types of (GC). The molecular mechanism underlying DGC IGC differences poorly understood. In this research, we carry out multilevel proteomic analyses, including proteome, phospho-proteome, transcription factor (TF) activity profiles, 196 cases covering in Chinese patients. Integrative proteogenomic analysis reveals ARIDIA mutation associated with opposite prognostic effects between IGC, via diverse influences on their corresponding proteomes. Systematical comparison consensus clustering identify three subtypes respectively, based distinct patterns cell cycle, extracellular matrix organization, immune response-related proteins expression. TF activity-based demonstrate that disease progressions were regulated by SWI/SNF NFKB complexes. Furthermore, inferred infiltration show Th1/Th2 ratio is an indicator for immunotherapeutic effectiveness, which validated independent GC anti-PD1 therapeutic patient group. Our analyses enable a more comprehensive understanding can further advance precision medicine.

Language: Английский

Citations

31
Integrative proteomic characterization of adenocarcinoma of esophagogastric junction DOI Creative Commons
Shengli Li, Yuan Li, Zhiyuan Xu

et al.

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

Published: Feb. 11, 2023

Abstract The incidence of adenocarcinoma the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics phosphoproteomics profiling 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing 94 tumor-NAT pairs, RNA 83 pairs. Our analysis reveals an extensively altered proteome 252 potential druggable proteins tumors. We identify three proteomic significant clinical differences. S-II subtype signature protein, FBXO44, is demonstrated to promote tumor progression metastasis vitro vivo. comparative analyses reveal distinct genomic features subtypes. find a specific decrease fibroblasts S-III subtype. Further phosphoproteomic comparisons different kinase-phosphosubstrate regulatory networks among proteogenomics dataset provides valuable resources for understanding mechanisms developing precision treatment strategies AEG.

Language: Английский

Citations

30
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

Citations

30