Identification of four gastric cancer subtypes based on genetic analysis of cholesterogenic and glycolytic pathways

Zhu, Zhou; Qin, Jian; Dong, Chen‐Cheng; Yang, Jin; Yang, Maughan; Tian, Jana; Zhong, Xiao

doi:10.1080/21655979.2021.1956247

Cited by 19 publications

(12 citation statements)

References 36 publications

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“…Previous research has revealed that metabolic grouping is associated with clinical and mutational profiles in multiple cancer types ( 20 , 21 ). We therefore sought to characterize the clinical relevance of the previously described metabolic subtypes in EGFR-WT NSCLC.…”

Section: Resultsmentioning

confidence: 99%

“…Karasinska et al constructed a stratification framework for pancreatic cancer based on the glycolytic/cholesterol cluster and found that patients with glycolytic tumors were associated with a worse prognosis in both resectable and metastatic pancreatic cancer ( 39 ). The stratification framework was also applied in other cancer types, but different correlations between metabolic subtypes and prognosis were observed in various cancer types ( 20 , 21 ). These studies reveal that glycolytic/cholesterol metabolic processes play different functional roles in oncogenesis and cancer progression.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non–small cell lung cancer

Mao¹,

Cai²,

Chen³

et al. 2022

JCI Insight

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Immune checkpoint blockade (ICB) therapy has achieved breakthroughs in the treatment of advanced non-small cell lung cancer (NSCLC). Nevertheless, the low response due to immuno-cold tumor microenvironment (TME) largely limits the application of ICB therapy. Based on the glycolytic/cholesterol synthesis axis, a stratification framework for EGFR wild-type NSCLC was developed to summarize the metabolic features of immuno-cold and immuno-hot tumors. The cholesterol subgroup displays the worst prognosis in immuno-cold NSCLC with significant enrichment of the cholesterol gene signature, indicating targeting cholesterol synthesis is essential for the therapy for immuno-cold NSCLC. Statin, the inhibitor for cholesterol synthesis, can suppress the aggressiveness of NSCLC in vitro and in vivo and also drastically reverse immuno-cold to an inflamed phenotype in vivo which exhibited a higher response to ICB therapy. Moreover, both our in-house data and meta-analysis further support that statin can significantly enhance ICB efficacy. In terms of preliminary mechanisms, statin could transcriptionally inhibit PD-L1 expression and induce ferroptosis in NSCLC cells. Overall, we reveal the significance of cholesterol synthesis in NSCLC and demonstrate the improved therapeutic efficacy of ICB in combination with statin.These findings could provide a innovative clinical insight to treat NSCLC patients with immuno-cold tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non–small cell lung cancer

Mao¹,

Cai²,

Chen³

et al. 2022

JCI Insight

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show abstract

“…Based on the mRNA expression values of the 26 HRGs, the samples were clustered by the “ ConsensusClusterPlus ” package of the R software [ 17 ].…”

Section: Methodsmentioning

confidence: 99%

Development of an Independent Prognostic Signature Based on Three Hypoxia-Related Genes for Breast Cancer

Wang

Guo

Zhang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Hypoxia was considered to be a prognostic indicator in a variety of solid tumors. This study aims at identifying the hypoxia-related genes (HRGs) in breast cancer (BC) and the feasibility of HRGs as a prognostic indicator. Methods. We downloaded the mRNA expression data of BC patients from TCGA and GEO databases. The LASSO Cox regression analysis was applied to screen the hub HRGs to establish a prognostic Risk Score. The independence of Risk Score was assessed by multivariate Cox regression analysis. And the immune checkpoint analysis was also performed. In addition, we also detected the expression level of hub HRGs in MCF-10A cells, MCF-7 cells, and SK-BR-3 cells by RT-qPCR. Results. Three HRGs were identified as hub genes with prognostic value in BC, including CA9, PGK1, and SDC1. The Risk Score constructed by these three genes could efficiently distinguish the prognosis of different BC patients and has been shown to be an independent prognostic indicator. In the high-risk group, patients had lower overall survival and poorer prognosis. In addition, the expression levels of five immune checkpoints (PD1, CTLA4, TIGIT, LAG3, and TIM3) in the high-risk group were significantly higher than those in the low-risk group. Moreover, the expression levels of PGK1 and SDC1 in BC cells were significantly increased. Conclusion. In this study, we established an efficiently model based on three optimal HRGs (CA9, PGK1, and SDC1) could clearly distinguish the prognosis of different BC patients.

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“…The abnormal expression of TP53 and MYC may facilitate the malignant progression of gastric cancer by facilitating cholesterol synthesis and affecting the use of cholesterol. From the genotyping of the metabolic genes of gastric cancer, differences may exist in patients subjected to different metabolic subtypes of gastric cancer in clinical characteristics (e.g., survival), and a clinically feasible gastric cancer grading scheme can be developed to guide the design of gastric cancer targeted therapy ( 74 ).…”

Section: Different Gastric Cancer Types Are Heterogenous In Terms Of ...mentioning

confidence: 99%

The Role of Lipid Metabolism in Gastric Cancer

Cui

Zhu

et al. 2022

Front. Oncol.

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Gastric cancer has been one of the most common cancers worldwide with extensive metastasis and high mortality. Chemotherapy has been found as a main treatment for metastatic gastric cancer, whereas drug resistance limits the effectiveness of chemotherapy and leads to treatment failure. Chemotherapy resistance in gastric cancer has a complex and multifactorial mechanism, among which lipid metabolism plays a vital role. Increased synthesis of new lipids or uptake of exogenous lipids can facilitate the rapid growth of cancer cells and tumor formation. Lipids form the structural basis of biofilms while serving as signal molecules and energy sources. It is noteworthy that lipid metabolism is capable of inducing drug resistance in gastric cancer cells by reshaping the tumor micro-environment. In this study, new mechanisms of lipid metabolism in gastric cancer and the metabolic pathways correlated with chemotherapy resistance are reviewed. In particular, we discuss the effects of lipid metabolism on autophagy, biomarkers treatment and drug resistance in gastric cancer from the perspective of lipid metabolism. In brief, new insights can be gained into the development of promising therapies through an in-depth investigation of the mechanism of lipid metabolism reprogramming and resensitization to chemotherapy in gastric cancer cells, and scientific treatment can be provided by applying lipid-key enzyme inhibitors as cancer chemical sensitizers in clinical settings.

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Identification of four gastric cancer subtypes based on genetic analysis of cholesterogenic and glycolytic pathways

Cited by 19 publications

References 36 publications

Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non–small cell lung cancer

Statin shapes inflamed tumor microenvironment and enhances immune checkpoint blockade in non–small cell lung cancer

Development of an Independent Prognostic Signature Based on Three Hypoxia-Related Genes for Breast Cancer

The Role of Lipid Metabolism in Gastric Cancer

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