Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer

Cheng, Yanan; Bu, Dechao; Zhang, Qiaoling; Sun, Rebecca; Lyle, Stephen; Zhao, Gang; Dong, Li; Li, Hui; Zhao, Yi; Yu, Jun; Hao, Xishan

doi:10.1016/j.jare.2022.10.019

Cited by 23 publications

(16 citation statements)

References 69 publications

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“…A large number of studies on various tumors have shown that patients with high TMB tend to have a good survival rate ( Cheng et al, 2022 ). Similarly, our study found that higher TMB was found in patients with low risk-score.…”

Section: Discussionmentioning

confidence: 99%

The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer

Chen

Mak

et al. 2023

Front. Cell Dev. Biol.

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Background: Gastric cancer (GC) is one of the most common malignancies in the human digestive tract. CD4+T cells can eliminate tumor cells directly through the mechanism of cytolysis, they can also indirectly attack tumor cells by regulating the tumor TME. A prognostic model of CD4+T cells is urgently needed to improve treatment strategies and explore the specifics of this interaction between CD4+T cells and gastric cancer cells. Methods: The detailed data of GC samples were downloaded from the Cancer Genome Atlas (TCGA), GSE66229, and GSE84437 datasets. CD4+ T cell-related genes were identified to construct a risk-score model by using the Cox regression method and validated with the Gene Expression Omnibus (GEO) dataset. In addition, postoperative pathological tissues of 139 gastric cancer patients were randomly selected for immunohistochemical staining, and their prognostic information were collected for external verification. Immune and molecular characteristics of these samples and their predictive efficacy in immunotherapy and chemotherapy were analysed.Results: The training set and validation set had consistent results, with GC patients of high PROC and SERPINE1 expression having poorer prognosis. In order to improve their clinical application value, we constructed a risk scoring model and established a high-precision nomogram. Low-risk patients had a better overall survival (OS) than high-risk patients, consistent with the results from the GEO cohort. Furthermore, the risk-score model can predict infiltration of immune cells in the tumor microenvironment of GC, as well as the response of immunotherapy. Correlations between the abundance of immune cells with PROC and SERPINE1 genes were shown in the prognostic model according to the training cohort. Finally, sensitive drugs were identified for patients in different risk subgroup.Conclusion: The risk model not only provides a basis for better prognosis in GC patients, but also is a potential prognostic indicator to distinguish the molecular and immune characteristics of the tumor, and its response to immune checkpoint inhibitor (ICI) therapy and chemotherapy.

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Section: Discussionmentioning

confidence: 99%

The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer

Chen

Mak

et al. 2023

Front. Cell Dev. Biol.

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“…Furthermore, we also found lipid homeostasis was correlated with tumor mutation burden (TMB) and chemotherapeutic effect. An analysis involving 206 GC patients and 435 cancer related genes was conducted to explore the prognostic value of TMB and mutational signatures in GC (Cheng et al 2022). Data from this research showed that TMB-high group had relatively worse prognosis, higher lipid metabolism activity and more frequent metabolic disorder, indicating immunotherapy combining metabolic inhibitors could be a novel treatment for GC.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Lipid Homeostasis Related Genes Signature in Predicting the Prognosis, Immunity, and Chemotherapeutic Effect for Patients With Gastric Cancer

Zhang

Han

et al. 2023

Preprint

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Purpose Gastric cancer (GC) is one of the most common cancers which causes millions of deaths annually. Lipids homeostasis is essential for the development of tumor because lipids metabolism is one of the most important metabolic reprogramming process within tumor. Elucidating the mechanism of lipids homeostasis in GC might significantly improve the treatment strategies and prognosis.Methods GSE62254 was applied to construct lipids homeostasis related genes signature (HGS) by multiple bioinformatic algorithms. HGS was successfully validated in TCGA-STAD and GSE84437. Besides, the correlations between HGS, immune/stromal cells infiltration and chemotherapeutic effect were analyzed as well.Result HGS was constructed based on eighteen lipids homeostasis related genes by WGCNA. Additionally, HGS was strongly associated with advanced TNM stages and it showed satisfactory value in predicting GC prognosis in three independent cohorts. Furthermore, we found HGS was associated with tumor mutation burden (TMB) and immune/stromal cells infiltration which were related with GC prognosis, indicating that lipids homeostasis had impact on the formation of tumor microenvironment (TME). In GSCAlite platform, PLOD2 and TGFB2 was proved to be positively related with chemotherapeutic resistance while SLC10A7 was a favorable factor for chemotherapy. Finally, CCK8 assay showed that disrupted lipids homeostasis could attenuate GC cell viability and specific genes expression levels were evaluated by RT-qPCR.Conclusion We identified a lipids homeostasis related genes signature which was correlated with the survival, clinical characteristics, TME, and chemotherapeutic of GC. This research provided a new perspective in improving prognosis and guiding individual chemotherapy for patients with GC.

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“…Surgery, radiotherapy, and chemotherapy are currently the main methods for the treatment of gastrointestinal tumors with obvious side effects ( Cheng et al, 2022 ). Betulinic acid has anticancer properties and is a biologically active compound present in the Betula tree.…”

Section: Ferroptosis In Cancersmentioning

confidence: 99%

Mechanism of ferroptosis in traditional chinese medicine for clinical treatment: A review

Liu

Jiang²,

He³

et al. 2023

Front. Pharmacol.

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Ferroptosis is an iron-dependent regulation of cell death driven by lipid peroxidation, which is intracellularly dependent on iron and independent of other metals, and morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. Ferroptosis is closely related to physiological and pathological processes, such as development, aging, and immunity, and it plays an important role in a variety of diseases. In many departments, traditional Chinese medicine plays an increasingly important role in their clinical treatment. In recent years, an increasing number of studies have been conducted on the mechanism of ferroptosis in traditional Chinese medicine. However, the role of ferroptosis in the clinical treatment of traditional Chinese medicine requires further exploration. This article mainly introduces the application of ferroptosis in studies of the mechanism of traditional Chinese medicine to help clinicians understand the current status of traditional Chinese medicine therapy for the treatment of ferroptosis-related diseases.

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Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer

Cited by 23 publications

References 69 publications

The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer

The predictive effect of immune therapy and chemotherapy under T cell-related gene prognostic index for Gastric cancer

Identification of a Lipid Homeostasis Related Genes Signature in Predicting the Prognosis, Immunity, and Chemotherapeutic Effect for Patients With Gastric Cancer

Mechanism of ferroptosis in traditional chinese medicine for clinical treatment: A review

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