Identification of a Tumor Microenvironment-relevant Gene set-based Prognostic Signature and Related Therapy Targets in Gastric Cancer DOI Creative Commons
Wangyu Cai,

Zi-Nan Dong,

Xiao-Teng Fu

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(19), P. 8633 - 8647

Published: Jan. 1, 2020

Rationale: The prognosis of gastric cancer (GC) patients is poor, and there limited therapeutic efficacy due to genetic heterogeneity difficulty in early-stage screening. Here, we developed validated an individualized gene set-based prognostic signature for (GPSGC) further explored survival-related regulatory mechanisms as well targets GC. Methods: By implementing machine learning, a model was established based on expression datasets from 1699 five independent cohorts with reported full clinical annotations. Analysis the tumor microenvironment, including stromal immune subcomponents, cell types, panimmune sets, immunomodulatory genes, carried out 834 GC three explore survival related GPSGC. To prove stability reliability GPSGC targets, multiplex fluorescent immunohistochemistry conducted tissue microarrays representing 186 patients. Based multivariate Cox analysis, nomogram that integrated other risk factors constructed two training verified by validation cohorts. Results: Through obtained optimal assessment model, GPSGC, which showed higher accuracy predicting than individual factors. impact score poor probably correlated remodeling components microenvironment. Specifically, TGFβ angiogenesis-related sets were significantly associated outcome. Immunomodulatory analysis combined experimental verification revealed TGFβ1 VEGFB may be potential according Furthermore, variables predict 3-year 5-year overall patients, improved characteristics only. Conclusion: As microenvironment-relevant signature, provides effective approach evaluate patient outcomes prolong enabling selection targeted therapy.

Language: Английский

Extracellular vesicles associated microRNAs: Their biology and clinical significance as biomarkers in gastrointestinal cancers DOI
Yuan Li,

Silei Sui,

Ajay Goel

et al.

Seminars in Cancer Biology, Journal Year: 2024, Volume and Issue: 99, P. 5 - 23

Published: Feb. 1, 2024

Language: Английский

Citations

12
The protective role of baicalin regulation of autophagy in cancers DOI Creative Commons
Qí Zhāng,

Shiyun Guo,

Han Ge

et al.

Cytotechnology, Journal Year: 2025, Volume and Issue: 77(1)

Published: Jan. 3, 2025

Language: Английский

Citations

1
LncRNA SNHG17 promotes gastric cancer progression by epigenetically silencing of p15 and p57 DOI
Guohua Zhang, Ying Xu,

Sijia Wang

et al.

Journal of Cellular Physiology, Journal Year: 2018, Volume and Issue: 234(4), P. 5163 - 5174

Published: Sept. 6, 2018

Abstract Long noncoding RNAs (lncRNA) are attractive biomarkers and therapeutic targets because of their disease‐ stage‐restricted expression. Small nucleolar RNA host gene 17 (SNHG17) belongs to a large family genes hosting small RNAs, with its expression pattern biological function not clarified in gastric cancer (GC). Thus, we conducted this study investigate the functional significance underlying mechanisms SNHG17 GC progression. Our results showed that was upregulated tissues cells, high significantly correlated increased invasion depth, lymphatic metastasis, advanced TNM stage. The plasma also found patients compared healthy controls, moderate accuracy for diagnosis (area under receiver operating characteristic curve = 0.748; 95% CI, 0.666–0.830). Gain‐ loss‐of‐function revealed promoted cell proliferation, cycle progression, invasion, migration inhibited apoptosis. Mechanistic investigations associated polycomb repressive complex 2 association required epigenetic repression cyclin‐dependent protein kinase inhibitors, including p15 p57, thus contributing regulation proliferation. Furthermore, rescue experiments indicated functioned as an oncogene via activating enhancer zeste homolog cells. provides new perspective acting tumorigenesis, it may serve novel early diagnostic marker potential target treatment GC.

Language: Английский

Citations

80
EGR1‐mediated linc01503 promotes cell cycle progression and tumorigenesis in gastric cancer DOI Creative Commons
Zhonghua Ma, Gao X, You Shuai

et al.

Cell Proliferation, Journal Year: 2020, Volume and Issue: 54(1)

Published: Nov. 3, 2020

Abstract Objectives Long non‐coding RNAs (lncRNAs) are key mediators in various malignancies. Linc01503 was previously elucidated to promote gastric cancer (GC) cell invasion. However, the upstream mechanism of linc01503 and its involvement GC cycle, apoptosis tumorigenesis still remain unclear. Materials Methods Bioinformatics analysis quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assays were implicated detect level GC. The role detected by vitro functional vivo xenograft tumour models. association between effector identified chromatin immunoprecipitation (ChIP) assays. mechanistic model clarified using subcellular separation, fluorescence situ hybridization, RNA‐sequencing, RNA (RIP) ChIP Results remarkably elevated tightly linked with overall survival patients factor early growth response protein 1 (EGR1) critically activated linc01503. Functionally, knockdown resulted activation G1/G0 phase arrest Mechanistically, interacted histone modification enzyme enhancer zeste 2 (EZH2) lysine (K)‐specific demethylase 1A (LSD1), thereby mediating transcriptional silencing dual‐specificity phosphatase 5 (DUSP5) cyclin‐dependent kinase inhibitor (CDKN1A) Conclusions EGR1‐activated could epigenetically silence DUSP5/CDKN1A expression mediate cycle progression tumorigenesis, implicating it as a prospective target for therapeutics.

Language: Английский

Citations

68
Identification of a Tumor Microenvironment-relevant Gene set-based Prognostic Signature and Related Therapy Targets in Gastric Cancer DOI Creative Commons
Wangyu Cai,

Zi-Nan Dong,

Xiao-Teng Fu

et al.

Theranostics, Journal Year: 2020, Volume and Issue: 10(19), P. 8633 - 8647

Published: Jan. 1, 2020

Rationale: The prognosis of gastric cancer (GC) patients is poor, and there limited therapeutic efficacy due to genetic heterogeneity difficulty in early-stage screening. Here, we developed validated an individualized gene set-based prognostic signature for (GPSGC) further explored survival-related regulatory mechanisms as well targets GC. Methods: By implementing machine learning, a model was established based on expression datasets from 1699 five independent cohorts with reported full clinical annotations. Analysis the tumor microenvironment, including stromal immune subcomponents, cell types, panimmune sets, immunomodulatory genes, carried out 834 GC three explore survival related GPSGC. To prove stability reliability GPSGC targets, multiplex fluorescent immunohistochemistry conducted tissue microarrays representing 186 patients. Based multivariate Cox analysis, nomogram that integrated other risk factors constructed two training verified by validation cohorts. Results: Through obtained optimal assessment model, GPSGC, which showed higher accuracy predicting than individual factors. impact score poor probably correlated remodeling components microenvironment. Specifically, TGFβ angiogenesis-related sets were significantly associated outcome. Immunomodulatory analysis combined experimental verification revealed TGFβ1 VEGFB may be potential according Furthermore, variables predict 3-year 5-year overall patients, improved characteristics only. Conclusion: As microenvironment-relevant signature, provides effective approach evaluate patient outcomes prolong enabling selection targeted therapy.

Language: Английский

Citations

65