Proteogenomic landscape of gastric adenocarcinoma peritoneal metastases

Zhao, Shuangtao; Wang, Ruiping; Song, Shumei; Hao, Dapeng; Han, Guangchun; Song, Xingzhi; Zhang, Jianhua; Pizzi, Melissa Pool; Shanbhag, Namita; Futreal, Andrew; Badgwell, Brian; Harada, Kazuto; Calin, George; Vykoukal, Jody; Yu, Chuan-Yih; Katayama, Hiroyuki; Hanash, Samir M.; Wang, Linghua; Ajani, Jaffer A.

doi:10.1016/j.isci.2023.106913

Cited by 2 publications

(3 citation statements)

References 41 publications

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“…These signatures included high rates of CDH1 and TP53 mutations, 6q loss and chr19 gain, chromosomal instability, and transcriptional upregulation of genes associated with cell cycle and immune tolerance. The demonstration of a "mesenchymal-like" subset of GC-PC, expressing epithelial to mesenchymal transition (EMT) phenotype and morphology with high expression of the checkpoint protein TIM-3 and its ligand (galectin-9), as well as TGF-β, reinforces the concept of immune evasion and tumor EMT as central features of GC-PC [38,39].…”

Section: Peritoneal Carcinomatosis As a Distinct Subtype Of Gastric C...mentioning

confidence: 72%

Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment

Lewis,

Dadgar,

Yellin

et al. 2023

Cancers

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Peritoneal carcinomatosis originating from gastric/gastroesophageal junction cancer (GC-PC) occurs in a defined subset of gastric cancer patients with unique clinical, pathologic, molecular and immunologic characteristics that create significant obstacles to effective treatment with modern therapy. Although systemic chemo- and immuno- therapy have yielded disappointing results in GC-PC, recent advances in the characterization of GC-PC and peritoneal immune biology present new opportunities for targeted therapeutics. In this review article, we discuss the distinct properties of GC-PC and the peritoneal immune environment as they pertain to current and investigative treatment strategies. We discuss pre-clinical studies and clinical trials relevant to the modulation of the peritoneal environment as a therapeutic intervention in GC-PC. Finally, we present a road map for future combinatorial strategies based on the conception of the peritoneal cavity as a bioreactor. Within this isolated compartment, prevailing immunosuppressive conditions can be altered through regional interventions toward an adaptive phenotype that would support the effectiveness of regionally delivered cellular therapy products. It is hoped that novel combination strategies would promote efficacy not only in the sequestered peritoneal environment, but also via migration into the circulation of tumor-reactive lymphocytes to produce durable systemic disease control, thereby improving oncologic outcome and quality of life in patients with GC-PC.

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Section: Peritoneal Carcinomatosis As a Distinct Subtype Of Gastric C...mentioning

confidence: 72%

Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment

Lewis,

Dadgar,

Yellin

et al. 2023

Cancers

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“…Meanwhile, diverse effects on corresponding proteomes were demonstrated, implying that diffuse-GC and intestinal-GC should be characterized based on multilevel data, including proteogenomics. More recently, comprehensive proteomic profiling using LC-MS has been applied to peritoneal carcinomatosis cells from GCs and compared with transcriptomic profiles [ 91 ]. Unsupervised hierarchical clustering analysis revealed three subgroups based on the extent of enrichment in cancer cells: Cluster A (tumor-cell enriched), Cluster B (tumor-immune mixed), and Cluster C (immune-cell enriched), which may be correlated with prognosis and drug response.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

“…When mutational profiles were integrated into proteomic data, many somatic mutations in driver genes and a higher tumor mutation burden were detected in Cluster A, while no somatic mutations were found in Cluster C. Pathway enrichment analysis displayed several enriched biological pathways (glycolysis, oxidative phosphorylation, TP53, MYC, mTORC1, TGF-β, neutrophil degranulation, neutrophil activation, neutrophil-mediated immunity, and cytokine production pathways) and several druggable targets (cancer-testis antigens, kinases, and receptors). Proteogenomic analysis revealed several genes with conflicting protein and mRNAs expression in peritoneal carcinomatosis cells, such as CTNNA2, LTF, CTAGE1, LAIR1, and HAVCR2, related to oncogenic, metabolic, and immune-related pathways, suggesting that combining proteomic and transcriptional analysis might result in a better understanding of the complex mechanisms affecting protein expression in peritoneal carcinomatosis from GC [ 91 ]. Potentially actionable therapeutic molecular targets will be detected using proteogenomic approaches to study more about the molecular composition of patients and their tumors.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Bioinformatics Analysis and Validation of Potential Markers Associated with Prediction and Prognosis of Gastric Cancer

Matsuoka,

Yashiro

2024

IJMS

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Gastric cancer (GC) is one of the most common cancers worldwide. Most patients are diagnosed at the progressive stage of the disease, and current anticancer drug advancements are still lacking. Therefore, it is crucial to find relevant biomarkers with the accurate prediction of prognoses and good predictive accuracy to select appropriate patients with GC. Recent advances in molecular profiling technologies, including genomics, epigenomics, transcriptomics, proteomics, and metabolomics, have enabled the approach of GC biology at multiple levels of omics interaction networks. Systemic biological analyses, such as computational inference of “big data” and advanced bioinformatic approaches, are emerging to identify the key molecular biomarkers of GC, which would benefit targeted therapies. This review summarizes the current status of how bioinformatics analysis contributes to biomarker discovery for prognosis and prediction of therapeutic efficacy in GC based on a search of the medical literature. We highlight emerging individual multi-omics datasets, such as genomics, epigenomics, transcriptomics, proteomics, and metabolomics, for validating putative markers. Finally, we discuss the current challenges and future perspectives to integrate multi-omics analysis for improving biomarker implementation. The practical integration of bioinformatics analysis and multi-omics datasets under complementary computational analysis is having a great impact on the search for predictive and prognostic biomarkers and may lead to an important revolution in treatment.

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Proteogenomic landscape of gastric adenocarcinoma peritoneal metastases

Cited by 2 publications

References 41 publications

Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment

Regional Immunotherapy for Peritoneal Carcinomatosis in Gastroesophageal Cancer: Emerging Strategies to Re-Condition a Maladaptive Tumor Environment

Bioinformatics Analysis and Validation of Potential Markers Associated with Prediction and Prognosis of Gastric Cancer

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