The circadian clock is associated with prognosis and immune infiltration in stomach adenocarcinoma

Huang, Zhihao; He, Aoxiao; Wang, Jiakun; Lü, Hongmei; Zhang, Rongguiyi; Wu, Linquan; Feng, Qian

doi:10.18632/aging.203184

Cited by 16 publications

(14 citation statements)

References 24 publications

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“…FN1 , SPARC , and SERPINE1 were highly expressed and significantly related to a poor prognosis of STAD ( Li et al, 2019 ). The high expressions of PER1 and NR1D1 were not only associated with poor OS, progression-free survival, and disease-free survival, but also associated with immune infiltration in STAD patients ( Huang et al, 2021 ). RNA binding protein genes such as PTBP1 , PPIH , SMAD5 , MSI2 , RBM15 , MRPS17 , and ADAT3 were identified to be prognosis-related in STAD patients, the regulatory network and functional study showed MRPS17 and PTBP1 could reduce the number of infiltrated immune cells.…”

Section: Introductionmentioning

confidence: 99%

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Liu

Tian

et al. 2022

Front. Genet.

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Background: Stomach adenocarcinoma (STAD) is one of the most frequently diagnosed cancers in the world with a poor prognosis due to genetic heterogeneity. The present study aimed to explore potential prognostic predictors and therapeutic targets that can be used for STAD treatment.Methods: We collected relevant data of STAD patients from the Cancer Genome Atlas (TCGA), including somatic mutation, transcriptome, and survival data. We performed a series of analyses such as tumor mutational burden (TMB), immune infiltration, and copy number variation (CNV) analysis to evaluate the potential mechanism of filaggrin (FLG) mutation in gastric cancer. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were performed for annotation of differentially expressed genes (DEGs). The STRING online database was used to construct the protein–protein interaction (PPI) and ceRNA network and hub genes were identified. Univariate and multivariate Cox regression analyses were used to determine the effect of selected DEGs on tumor prognosis.Results: The FLG-mutant group (FLG-MT) showed a higher mutation load and immunogenicity in gastric cancer. GO and KEGG analyses identified and ranked unique biologic processes and immune-related pathway maps that correlated with the FLG-mutant target. GSEA analysis showed that several tumorigenesis and metastasis-related pathways were indeed enriched in FLG-mutant tumor tissue. Both cell cycle–related pathways and the DNA damage and repair associated pathways were also enriched in the FLG-MT group. The FLG mutations resulted in increased gastric cancer sensitivity to 24 chemotherapeutic drugs. The ceRNA network was established using Cytoscape and the PPI network was established in the STRING database. The results of the prognostic information further demonstrated that the OS and DFS were significantly higher in FLG mutation carriers, and the FLG gene mutation might be a protective factor.Conclusion: The multiple molecular mechanisms of the FLG gene in STAD are worthy of further investigation and may reveal novel therapeutic targets and biomarkers for STAD treatment.

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Section: Introductionmentioning

confidence: 99%

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Liu

Tian

et al. 2022

Front. Genet.

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“…Another recent report has demonstrated that CST2 overexpression was closely connected with the cell proliferation and migration as well as TGF-β signalling pathway (32), which coincided with our GSEA results in three datasets (Figure 5A-5C). NR1D1 encodes a transcription factor that negatively regulates the expression of core clock proteins, which is associated with immune cell infiltration in stomach adenocarcinoma (33), and OLFML2B was reported to be correlated with poor prognosis of GC (32,34). However, the functions of the remaining four genes, CPNE8, HTR1F, NTAN1, and TMEM259, necessitate further study.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of cancer-associated fibroblast related gene signature as a predictive model in clinical outcomes and immune characteristics of gastric cancer

Zhang¹,

Zhang²,

Fu³

et al. 2022

Ann Transl Med

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Background: Gastric cancer (GC) has a high incidence and high mortality rate among Asian countries, and distinguishing predictive prognosis biomarkers for GC are essential. Cancer-associated fibroblasts (CAFs) play a significant role in the progression, immune evasion, and therapeutic resistance of GC. Therefore, CAF-associated genes might have huge potential as prognostic biomarkers for predicting tumor progression and survival rate in GC pateints.Methods: A sum of 1,134 GC patients from the The Cancer Genome Atlas Stomach Adenocarcinoma (TCGA-STAD), GSE62254, and GSE84437 datasets as well as GC cohorts from Xijing hospital were included. Firstly, we performed univariate Cox regression analysis to identify CAF-associated prognostic genes. Subsequently, the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was used to develop a CAF gene signature (CAFGS) in the TCGA-STAD training cohort. CAFGS's predictive performance was examined in both the training and validation cohorts, and the relationship between CAFGS and the tumor microenvironment (TME) was investigated by ssGSEA, CIBERSORT, TIMER, and ESTIMATE. Finally, a nomogram of CAFGS was established.Results: Ten CAF-associated genes (ANGPTL4, CPNE8, CST2, HTR1F, IL1RAP, NR1D1, NTAN1, OLFML2B, TMEM259, and VTN) were identified to develop CAFGS. A high CAFGS score represented a worse outcome for GC patients in four cohorts, and a strong correlation was found between CAFGS and the infiltration of immune cells. We showed that CAFs contribute to immune evasion and unfavorable prognoses of GC patients by promoting the formation of an immunosuppressive microenvironment, and a high level of CAF infiltration may attenuate the efficacy of immunotherapy. The nomogram based on CAFGS showed reasonable predictive ability and may deliver great clinical net benefits. Conclusions:We established a CAFGS model with 10 CAF-associated genes that had a great predictive ^ ORCID: 0000-0001-7059-6995.

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“…As a result, 9 identified MRGs were adopted for building the MRGS. The mRNA level of NR1D1 was upregulated in STAD tissues when compared with normal tissues [ 33 ]. The prognosis of STAD patients likely benefited from lower expression levels of KYNU [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of a Metabolic Reprogramming-Associated Risk Model Related to Prognosis, Immune Microenvironment, and Immunotherapy of Stomach Adenocarcinoma

Zhao

Zhang

Sun

2022

Journal of Oncology

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Stomach adenocarcinoma (STAD) is one of the most common malignant digestive tumors. Metabolic reprogramming is an essential feature of tumorigenesis. The roles of metabolic reprogramming in STAD patients were investigated to explore the tumor immune microenvironment (TME) and potential therapeutic strategies. STAD samples’ transcriptomic and clinical data were collected from The Cancer Genome Atlas (TCGA) set and the GSE84437 set. The signature based on the metabolism-related genes (MRGs) was built using the Cox regression model to predict prognosis in STAD. Notably, this MRG-based signature (MRGS) accurately predicted STAD patients’ clinical survival in multiple datasets and could serve as an indicator independently. STAD patients with high scores on the MRGS were eligible for generating a type I/II interferon (IFN) response, according to a complete examination of the link between the MRGS and TME. Tumor Immune Dysfunction and Exclusion (TIDE) and immunophenoscore (IPS) analyses revealed that STAD patients with different MRGS scores had different reactions to immunotherapy. Consequently, assessing the pattern of these MRGs increases the understanding of TME features in STAD, hence directing the development of successful immunotherapy regimens.

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The circadian clock is associated with prognosis and immune infiltration in stomach adenocarcinoma

Cited by 16 publications

References 24 publications

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Association of FLG mutation with tumor mutation load and clinical outcomes in patients with gastric cancer

Bioinformatic analysis of cancer-associated fibroblast related gene signature as a predictive model in clinical outcomes and immune characteristics of gastric cancer

Identification of a Metabolic Reprogramming-Associated Risk Model Related to Prognosis, Immune Microenvironment, and Immunotherapy of Stomach Adenocarcinoma

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