Senescence-related genes define prognosis, immune contexture, and pharmacological response in gastric cancer DOI Creative Commons
Xiaogang Shen, Meng Wang, Wenxi Chen

et al.

Aging, Journal Year: 2023, Volume and Issue: unknown

Published: Feb. 16, 2023

As one of the prevalent tumors worldwide, gastric cancer (GC) has obtained sufficient attention in its clinical management and prognostic stratification. Senescence-related genes are involved tumorigenesis progression GC. A machine learning algorithm-based signature was developed from six senescence-related including SERPINE1, FEN1, PDGFRB, SNCG, TCF3, APOC3. The TCGA-STAD cohort utilized as a training set while GSE84437 GSE13861 cohorts were analyzed for validation. Immune cell infiltration immunotherapy efficacy investigated PRJEB25780 cohort. Data genomics drug sensitivity (GDSC) database revealed pharmacological response. GSE54129 cohorts, single-cell dataset GSE134520, Human Protein Atlas (THPA) localization key genes. Association higher risk-score with worse overall survival (OS) identified (TCGA-STAD, P<0.001; HR = 2.03, 95% CI, 1.45–2.84) validation (GSE84437, P 0.005; 1.48, 1.16–1.95; GSE13861, 0.03; 2.23, 1.07–4.62). positively correlated densities tumor-infiltrating immunosuppressive cells (P < 0.05) lower patients who responded to pembrolizumab monotherapy 0.03). Besides, high had sensitivities inhibitors against PI3K-mTOR angiogenesis 0.05). Expression analysis verified promoting roles suppressing APOC3 SNCG GC, respectively. Immunohistochemistry staining their location potential origins. Taken together, senescence gene-based model may potentially change GC by enabling risk stratification predicting response systemic therapy.

Language: Английский

The Pyroptosis-Related Signature Predicts Prognosis and Indicates Immune Microenvironment Infiltration in Gastric Cancer DOI Creative Commons
Wei Shao, Zongcheng Yang, Yue Fu

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: June 11, 2021

Gastric cancer (GC) is one of the leading causes cancer-related deaths and shows high levels heterogeneity. The development a specific prognostic model important if we are to improve treatment strategies. Pyroptosis can arise in response H. pylori , primary carcinogen, also chemotherapy drugs. However, evaluation GC pyroptosis insufficient. Consensus clustering by pyroptosis-related regulators was used classify 618 patients with from four GEO cohorts. Following Cox regression differentially expressed genes, our prognosis (PS-score) built LASSO-Cox analysis. TCGA-STAD cohort as validation set. ESTIMATE, CIBERSORTx, EPIC were investigate tumor microenvironment (TME). Immunotherapy cohorts blocking PD1 / PD-L1 response. subtyping based on able according different clinical traits TME. difference between two subtypes identified this study develop which named “PS-score.” PS-score could predict his/her overall survival time. A low implies greater inflammatory cell infiltration better immunotherapy blockers. Our findings provide foundation for future research targeting its immune responses immunotherapy.

Language: Английский

Citations

159
Review: RNA-based diagnostic markers discovery and therapeutic targets development in cancer DOI
Hongbo Wang, Qinghai Meng, Jinjun Qian

et al.

Pharmacology & Therapeutics, Journal Year: 2022, Volume and Issue: 234, P. 108123 - 108123

Published: Feb. 1, 2022

Language: Английский

Citations

81
Application of artificial intelligence for improving early detection and prediction of therapeutic outcomes for gastric cancer in the era of precision oncology DOI
Zhe Wang, Yang Liu, Xing Niu

et al.

Seminars in Cancer Biology, Journal Year: 2023, Volume and Issue: 93, P. 83 - 96

Published: April 27, 2023

Language: Английский

Citations

45
Artificial Intelligence in Gastrointestinal Cancer Research: Image Learning Advances and Applications DOI Creative Commons
Shengyuan Zhou, Yi Xie,

Xujiao Feng

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: 614, P. 217555 - 217555

Published: Feb. 12, 2025

Language: Английский

Citations

2
Identification of a Tumor Immunological Phenotype-Related Gene Signature for Predicting Prognosis, Immunotherapy Efficacy, and Drug Candidates in Hepatocellular Carcinoma DOI Creative Commons
Yuqin Tang,

Chengbin Guo,

Yang Zhao

et al.

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: April 12, 2022

Hepatocellular carcinoma (HCC) is the predominant subtype of primary liver cancer and represents a highly heterogeneous disease, making it hard to predict prognosis therapy efficacy. Here, we established novel tumor immunological phenotype-related gene index (TIPRGPI) consisting 11 genes by Univariate Cox regression least absolute shrinkage selection operator (LASSO) algorithm HCC immunotherapy response. TIPRGPI was validated in multiple datasets exhibited outstanding performance predicting overall survival HCC. Multivariate analysis verified as an independent predictor TIPRGPI-integrated nomogram constructed provide quantitative tool for clinical practice. Distinct mutation profiles, hallmark pathways, infiltration immune cells microenvironment were shown between high low-risk groups. Notably, significant differences immunogenicity dysfunction exclusion (TIDE) observed two risk groups, suggesting better response checkpoint blockade (ICB) group. Besides, six potential drugs binding core target signature predicted via molecular docking. Taken together, our study shows that proposed reliable classification, response, candidate with application decision treatment The “TIP genes”-guided strategy efficacy, reported here, might be also applied more cancers other than

Language: Английский

Citations

36
Senescence as a dictator of patient outcomes and therapeutic efficacies in human gastric cancer DOI Creative Commons

Lulin Zhou,

Zubiao Niu,

Yuqi Wang

et al.

Cell Death Discovery, Journal Year: 2022, Volume and Issue: 8(1)

Published: Jan. 10, 2022

Senescence is believed to be a pivotal player in the onset and progression of tumors as well cancer therapy. However, guiding roles senescence clinical outcomes therapy selection for patients with remain obscure, largely due absence feasible signature. Here, by integrative analysis single cell bulk transcriptome data from multiple datasets gastric patients, we uncovered veiled tumor feature characterized gene signature enriched, unexpectedly, noncancerous cells, further identified two distinct senescence-associated subtypes based on unsupervised clustering. Patients subtype had higher mutation loads better prognosis compared aggressive subtype. By machine learning, constructed scoring system termed senescore six genes: ADH1B, IL1A, SERPINE1, SPARC, EZH2, TNFAIP2. Higher demonstrated robustly predictive capability longer overall recurrence-free survival 2290 samples, which was independently validated multiplex staining samples tissue microarray. Remarkably, served reliable predictor chemotherapeutic immunotherapeutic efficacies, high-senescore benefited immunotherapy, while low-senescore were responsive chemotherapy. Collectively, report heretofore unrecognized hallmark that impacts patient therapeutic efficacy.

Language: Английский

Citations

36
Cancer Stem Cells and the Tumor Microenvironment in Gastric Cancer DOI Creative Commons
Ying Yang, Wenjian Meng, Ziqiang Wang

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 3, 2022

Gastric cancer (GC) remains one of the leading causes cancer-related death worldwide. Cancer stem cells (CSCs) might be responsible for tumor initiation, relapse, metastasis and treatment resistance GC. The microenvironment (TME) comprises cells, immune stromal other extracellular components, which plays a pivotal role in progression therapy resistance. properties CSCs are regulated by matrix components TME some unique manners. This review will summarize current literature regarding effects on GC, while emphasizing potential developing successful anti-tumor based targeting CSCs.

Language: Английский

Citations

35
Comprehensive Analysis of Immune Implications and Prognostic Value of SPI1 in Gastric Cancer DOI Creative Commons
Jianfeng Huang, Wenzheng Chen, Zhigang Jie

et al.

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

Published: Feb. 14, 2022

The transcription factor Spi-1 proto-oncogene (SPI1, also known as PU.1) is a key regulator of signal communication in the immune system and essential for development myeloid cells lymphocytes. However, potential role SPI1 gastric cancer (GC) correlations between infiltration remain unclear.In present study, multiple databases including ONCOMINE, TIMER, Kaplan-Meier Plotter, Cancer Genome Atlas were used to explore expression levels prognostic value GC. cBioPortal was possible reasons increased tumor-infiltrating (TICs) analyzed using CIBERSORT TIMER. Gene set enrichment analysis determine biological function In addition, risk signature based on SPI1-related immunomodulators constructed accurately evaluate prognosis patients with upregulation GC further confirmed through immunohistochemistry, western blotting, real-time quantitative PCR (RT-qPCR) assay.The significantly according databases, high related poor progression main influencing mRNA may be diploidy, not DNA methylation. Moreover, RT-qPCR assays upregulated revealed that correlated seven types TICs (naive B cells, resting memory CD4 T activated natural killer M2 macrophages, dendritic cells). indicated might activation participate cell cycle regulation. immunomodulators, we developed multiple-gene prediction signatures nomogram can independently predict clinical outcome GC.The results study suggest has critical determining immunotherapeutic target.

Language: Английский

Citations

26
Wnt signaling in gastric cancer: current progress and future prospects DOI Creative Commons
Ruyue Han, Jing Yang, Yingying Zhu

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 7, 2024

Levels of the Wnt pathway components are abnormally altered in gastric cancer cells, leading to malignant cell proliferation, invasion and metastasis, poor prognosis chemoresistance. Therefore, it is important understand mechanism signaling cancer. We systematically reviewed molecular mechanisms development; summarize progression challenges research on agents pathway.

Language: Английский

Citations

5
Use of machine learning-based integration to develop an immune-related signature for improving prognosis in patients with gastric cancer DOI Creative Commons

Jingyuan Ning,

Keran Sun,

Xiaoqing Fan

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: April 29, 2023

Abstract Gastric cancer is one of the most common malignancies. Although some patients benefit from immunotherapy, majority have unsatisfactory immunotherapy outcomes, and clinical significance immune-related genes in gastric remains unknown. We used single-sample gene set enrichment analysis (ssGSEA) method to evaluate immune cell content TCGA clustered based on scores. The Weighted Correlation Network Analysis (WGCNA) algorithm was identify subtype-related genes. were randomly divided into test 1 2 a 1:1 ratio, machine learning integration process determine best prognostic signatures total cohort. then validated Based literature search, we selected 93 previously published for compared them with our signatures. At single-cell level, algorithms "Seurat," "SCEVAN", "scissor", "Cellchat" demonstrate communication disturbance high-risk cells. WGCNA univariate Cox regression identified 52 prognosis-related genes, which subjected 98 machine-learning processes. A signature consisting 24 using StepCox[backward] Enet[alpha = 0.7] algorithms. This demonstrated performance overall, test1 test2 cohort, outperformed Interaction perturbations cellular T cells at may promote disease progression cancer. developed an reliable validity high accuracy use predicting prognosis

Language: Английский

Citations

11