• TIM-3
• glioblastoma
• immunosuppression

• Humans
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Glioblastoma/genetics
• Hepatitis A Virus Cellular Receptor 2/metabolism
• Disease Progression
• Animals
• Brain Neoplasms/metabolism
• Brain Neoplasms/pathology
• Brain Neoplasms/genetics

• cns cancer

• Humans
• Perilipin-1/metabolism
• Perilipin-1/genetics
• Glioma/genetics
• Glioma/pathology
• Glioma/metabolism
• Lipid Metabolism/genetics
• Cell Line, Tumor
• Disease Progression
• Brain Neoplasms/genetics
• Brain Neoplasms/pathology
• Brain Neoplasms/metabolism
• Phosphatidylinositol 3-Kinases/metabolism
• Animals
• Cell Proliferation
• Proto-Oncogene Proteins c-akt/metabolism
• Mice, Nude
• Mice
• Gene Expression Regulation, Neoplastic
• Male
• Signal Transduction
• Female
• Neoplasm Invasiveness
• Cell Movement/genetics
• Down-Regulation/genetics

• 2022JJ30904 Natural Science Foundation of Hunan Province (Hunan Provincial Natural Science Foundation)
• Changsha Municipal Natural Science Foundation (kq2202431)

• HNSCC
• LASSO
• OSCC
• chemotherapy
• gene signature
• immunotherapy
• prognosis

• ACAT1
• ACSL3
• biomarker
• fatty acid metabolism
• lung adenocarcinoma
• qRT‐PCR

• Humans
• Lung Neoplasms/genetics
• Lung Neoplasms/pathology
• Lung Neoplasms/metabolism
• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Prognosis
• Fatty Acids/metabolism
• Adenocarcinoma of Lung/genetics
• Adenocarcinoma of Lung/immunology
• Adenocarcinoma of Lung/metabolism
• Adenocarcinoma of Lung/pathology
• Adenocarcinoma of Lung/mortality
• Gene Expression Regulation, Neoplastic
• Male
• Female
• Coenzyme A Ligases/genetics
• Coenzyme A Ligases/metabolism
• Immunotherapy/methods
• Middle Aged
• Gene Expression Profiling/methods

• ZKX21015 Key Project of Nanjing Medical Science and Technology Program

• B7-H3
• cancer therapy
• non-immune functions
• tumor cells
• tumor vasculature

• HOPX
• LGG
• PHEX
• SHANK2
• Tumor immunology
• and LGALS1
• fatty acid metabolism
• prognostic features

• Fatty acids
• Immunotherapy
• Metabolism
• Risk assessment
• Stomach neoplasms

The prognosis of gastric cancer is extremely poor. Metabolic reprogramming involving lipids has been associated with cancer occurrence and progression.

To illustrate fatty acid metabolic mechanisms in gastric cancer, detect core genes, develop a prognostic model, and provide treatment options.

Raw data from The Cancer Genome Atlas and Gene Expression Omnibus databases were collected and analyzed. Differentially expressed fatty acid metabolism genes were identified and incorporated into a risk model based on least absolute shrinkage and selection operator regression analysis. Then, patients from The Cancer Genome Atlas were assigned to high- and low-risk cohorts according to the mean value of the risk score as the threshold, which was verified in the Gene Expression Omnibus database. Relationships between chemotherapeutic sensitivity and tumor microenvironment features were assessed.

An integrated evaluation was performed in this study. Fatty acid metabolism-related genes were used to construct the risk model. Patients classified into the high-risk cohort were considered to be resistant to chemotherapy based on results of the “pRRophetic” R package. Patients in the high-risk cohort were associated with type I/II interferon activation, increased inflammation level, immune cell infiltration, and tumor immune dysfunction based on the exclusion algorithm, indicating the potential benefit of immunotherapy in these patients.

We constructed a fatty acid-related risk score model to assess the comprehensive fatty acid features in gastric cancer and validated its vital role in prognosis, chemotherapy sensitivity, and immunotherapy.

• Stomach neoplasms
• Fatty acids
• Metabolism
• Risk assessment
• Immunotherapy

• Bioinformatics analysis
• Competing endogenous RNA networks
• Lipid metabolism
• Long non-coding RNA
• Osteosarcoma

• 202005AD160146 Technical Innovation Talents Training Object Project
• 202102AA310068 Grants from Yunnan Orthopedics and Sports Rehabilitation Clinical Medicine Research Center
• ZX20191001 Yunnan Traumatology and Orthopedics Clinical Medical Center

• Fatty acid metabolism
• Prognosis
• Prostate cancer
• Tumorigenesis

• Fatty acid metabolism
• Immune infiltration
• Prognostic model
• Prostate cancer
• Recurrence free survival

• cutaneous melanoma
• fatty acid metabolism
• immune checkpoint
• immune infiltration
• prognosis
• tumor metabolism
• tumor microenvironment

• Humans
• Melanoma/genetics
• Skin Neoplasms/genetics
• Programmed Cell Death 1 Receptor
• Biomarkers
• Fatty Acids
• Tumor Microenvironment/genetics
• L-Amino Acid Oxidase

Background: Esophageal cancer (ESCA) is a major cause of cancer-related mortality worldwide. Altered fatty acid metabolism is a hallmark of cancer. However, studies on the roles of fatty acid metabolism-related genes (FRGs) in ESCA remain limited. Method: We identified differentially expressed FRGs (DE-FRGs). Then, the DE-FRGs prognostic model was constructed and validated using a comprehensive analysis. Moreover, the correlation between the risk model and clinical characteristics was investigated. A nomogram for predicting survival was established and evaluated. Subsequently, the difference in tumor microenvironment (TME) was compared between two risk groups. The sensitivity of key DE-FRGs to chemotherapeutic interventions and their correlation with immune cells were investigated. Finally, DEGs between two risk groups were measured and the prognostic value of key DE-FRGs in ESCA was confirmed in other databases. Results: A prognostic model was constructed based on seven selected DEG-FRGs. TNM staging and CD8+ T cells were significantly correlated with high-risk groups. Low-risk groups exhibited more infiltrated M0 macrophages, an activation of type II interferon (IFN-γ) responses, and were found to be more suitable for immunotherapy. Seven key DE-FRGs with prognostic value were found to be considerably influenced by different chemotherapy drugs. Conclusion: A prognostic model based on seven DE-FRGs may efficiently predict patient prognosis and immunotherapy response, helping to develop individualized treatment strategies in ESCA.

• The Cancer Genome Atlas (TCGA)
• esophageal cancer (ESCA)
• fatty acid metabolism
• immunotherapy response
• prognosis

Clear Cell Renal Cell Carcinoma (ccRCC) is the most common and aggressive subtype of renal cancer. Abnormal fatty acid metabolism (FAM) is reported to be strongly associated with multiple malignancies, yet there is limited research in ccRCC. In this manuscript, we reported the significant role of abnormal FAM in predicting the prognosis of ccRCC. Three independent clinical cohorts (TCGA, EMTAB and our clinical cohorts with prognostic profiles and gene expression data, including RNA-seq, microarray and RT-qPCR) were applied as training and two external validation cohorts. As a result, we successfully constructed and validated a novel FAM-related gene signature (FAMGS) and nomogram for the overall survival of patients with ccRCC. Additionally, our study further elucidated the potential immune relevance and molecular mechanisms of abnormal FAM and the signature. In conclusion, the novel FAMGS constructed in this study offered a promising prognostic tool in clinic and potential therapeutic targets for ccRCC patients.

This study aims to explore the role of abnormal fatty acid metabolism (FAM) in ccRCC and construct a novel fatty acid metabolism-related gene signature (FAMGS) for prognosis. Three independent ccRCC cohorts, including The Cancer Genome Atlas, E-MTAB-1980 and our clinical cohort (including RNA-seq, microarray and RT-qPCR data), were applied as training and two independent validation cohorts. Firstly, FAM levels were found to be significantly decreased in ccRCC and correlated with degrees of malignancy, confirming the pivotal role of FAM in ccRCC. Applying the least absolute shrinkage and selection operator cox regression, we established a novel FAMGS for overall survival (OS). The FAMGS divided patients into low or high-risk groups in the training cohort and were successfully validated in both the EMTAB and our clinical validation cohorts. Additionally, the FAMGS serves as an independent risk factor for OS of ccRCC. Results of the immune cell abundance identifier (ImmuCellAI) algorithm and gene set variation analysis (GSVA) revealed that patients in the high-risk group have comprehensively impaired metabolism, including lipids, amino acids and tricarboxylic acid cycle-related pathways and a more immunosuppressive tumor microenvironment. In conclusion, our study constructed and validated a novel FAMGS, which may improve the risk stratification optimization and personalized management of ccRCC.

• clear cell renal cell carcinoma
• fatty acid metabolism
• gene signature
• nomogram
• prognosis

Fatty acid (FA) metabolism is considered the emerging cause of tumor development and metastasis, driving poor prognosis. Long non-coding RNAs (lncRNAs) are closely related to cancer progression and play important roles in FA metabolism. Thus, the discovery of FA metabolism-related lncRNA signatures to predict outcome and immunotherapy response is critical in improving the survival of patients with hepatocellular carcinoma (HCC).

FA metabolism scores and a FA metabolism-related lncRNA signature were constructed using a single-sample gene set enrichment analysis based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. “ConsensusClusterPlus” was used to screen molecular subtypes. Chi-squared test and Fisher’s exact test were applied to explore the relationship between clinical, genomic mutation characteristics and subtypes. Transcription factor (TF) activity scores, cellular distributions, immune cell infiltration, and immunotherapy response were employed to investigate the functions of FA metabolism-related lncRNA signatures. FA metabolism microarray and western blot were performed to detect the biological function of candidate lncRNAs.

A total of 70 lncRNAs that highly correlated with FA metabolism scores in two cohorts were used to construct two distinct clusters. Patients in cluster 2 had lower FA metabolism scores and worse survival than those in cluster 1. Patients in cluster 2 exhibited a high frequency of DNA damage, gene mutations, oncogenic signaling such as epithelial-to-mesenchymal transition, and a high degree of immune cell infiltration. Moreover, the lncRNA signature could predict the effects of immunotherapy in patients with HCC. Furthermore, three lncRNAs (SNHG1, LINC00261, and SNHG7) were identified that were highly correlated with FA metabolism. Additionally, SNHG1 and SNHG7 were found to regulate various FA metabolism-related genes and ferroptosis-related genes in vitro experiments. GSEA analysis revealed that SNHG1 and SNHG7 promote fatty acid beta-oxidation. SNHG1 and SNHG7 silencing dramatically reduced lipid droplets in HCC cells. Many immune-infiltration genes and TFs were overexpressed in HCC tissues with SNHG1 and SNHG7 high expression.

A novel molecular model of FA metabolism-related lncRNAs was developed, which has significantly prognostic potential in HCC diagnosis and aids in clinical decision making.

The online version contains supplementary material available at 10.1186/s12885-022-10122-4.

• Fatty acid metabolism
• Ferroptosis
• Hepatocellular carcinoma
• Immune infiltrations
• LncRNA

• Unsaturated fatty acids biosynthesis
• colon cancer
• multi-omics characterization
• overall survival
• prognostic signature

Glioblastoma multiforme (GBM), a highly invasive and incurable tumor, is the humans’ foremost, commonest, and deadliest brain cancer. As in other cancers, distinct combinations of genetic alterations (GA) in GBM induce a diversity of metabolic phenotypes resulting in enhanced malignancy and altered sensitivity to current therapies. Furthermore, GA as a hallmark of cancer, dysregulated cell metabolism in GBM has been recently linked to the acquired GA. Indeed, Numerous point mutations and copy number variations have been shown to drive glioma cells’ metabolic state, affecting tumor growth and patient outcomes. Among the most common, IDH mutations, EGFR amplification, mutation, PTEN loss, and MGMT promoter mutation have emerged as key patterns associated with upregulated glycolysis and OXPHOS glutamine addiction and altered lipid metabolism in GBM. Therefore, current Advances in cancer genetic and metabolic profiling have yielded mechanistic insights into the metabolism rewiring of GBM and provided potential avenues for improved therapeutic modalities. Accordingly, actionable metabolic dependencies are currently used to design new treatments for patients with glioblastoma. Herein, we capture the current knowledge of genetic alterations in GBM, provide a detailed understanding of the alterations in metabolic pathways, and discuss their relevance in GBM therapy.

• Fondation OCP

• fatty acid metabolism
• glioma
• prognosis
• signature
• tumor microenvironment

• Fatty Acids
• Gene Expression Regulation, Neoplastic
• Glioma/genetics
• Glioma/metabolism
• Glioma/therapy
• Humans
• Immunotherapy
• Prognosis
• Tumor Microenvironment/genetics

• National Natural Science Foundation of China

Background: Emerging molecular and genetic biomarkers have been introduced to classify gliomas in the past decades. Here, we introduced a risk signature based on the cellular response to the IL-4 gene set through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Methods: In this study, we provide a bioinformatic profiling of our risk signature for the malignancy, prognosis and immune phenotype of glioma. A cohort of 325 patients with whole genome RNA-seq expression data from the Chinese Glioma Genome Atlas (CGGA) dataset was used as the training set, while another cohort of 667 patients from The Cancer Genome Atlas (TCGA) dataset was used as the validating set. The LASSO model identified a 10-gene signature which was considered as the optimal model. Results: The signature was confirmed to be a good predictor of clinical and molecular features involved in the malignancy of gliomas. We also identified that our risk signature could serve as an independently prognostic biomarker in patients with gliomas (p < 0.0001). Correlation analysis showed that our risk signature was strongly correlated with the Tregs, M0 macrophages and NK cells infiltrated in the microenvironment of glioma, which might be a supplement to the existing incomplete innate immune mechanism of glioma phenotypes. Conclusions: Our IL-4-related gene signature was associated with more aggressive and immunosuppressive phenotypes of gliomas. The risk score could predict prognosis independently in glioma, which might provide a new insight for understanding the IL-4 involved mechanism of gliomas.

Abnormal metabolism, including abnormal fatty acid metabolism, is an emerging hallmark of cancer. The current study sought to investigate the potential prognostic value of fatty acid metabolism-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). To this end, we obtained the gene expression data and clinical data of patients with CRC from The Cancer Genome Atlas (TCGA) database. Through gene set variation analysis (GSVA), we found that the fatty acid metabolism pathway was related to the clinical stage and prognosis of patients with CRC. After screening differentially expressed RNAs, we constructed a fatty acid metabolism-related competing endogenous RNA (ceRNA) network based on the miRTarBase, miRDB, TargetScan, and StarBase databases. Next, eight fatty acid metabolism-related lncRNAs included in the ceRNA network were identified to build a prognostic signature with Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, and a nomogram was established based on the lncRNA signature and clinical variables. The signature and nomogram were further validated by Kaplan–Meier survival analysis, Cox regression analysis, calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA). Besides, the TCGA internal and the quantitative real-time polymerase chain reaction (qRT-PCR) external cohorts were applied to successfully validate the robustness of the signature and nomogram. Finally, in vitro assays showed that knockdown of prognostic lncRNA TSPEAR-AS2 decreased the triglyceride (TG) content and the expressions of fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) in CRC cells, which indicated the important role of lncRNA TSPEAR-AS2 in modulating fatty acid metabolism of CRC. The result of Oil Red O staining showed that the lipid content in lncRNA TSPEAR-AS2 high expression group was higher than that in lncRNA TSPEAR-AS2 low expression group. Our study may provide helpful information for fatty acid metabolism targeting therapies in CRC.

• ceRNA network
• colorectal cancer
• fatty acid metabolism
• long noncoding RNA
• nomogram
• signature

To screen glycolytic genes linked to the glioma prognosis and construct the prognostic model.

The relevant data of glioma were downloaded from TCGA and GTEx databases. GSEA of glycolysis-related pathways was carried out, and enriched differential genes were extracted. Screening out prognostic-related genes with conspicuous significance and construction of the prognostic model were conducted by multivariate Cox regression analysis and Lasso regression analysis. The model was evaluated, and cBioPortal was used to analyze the mutation of the model gene. The expression of the model gene in tumor and normal colon tissue was analyzed. The model was used to evaluate the prognosis of patients in different groups to verify the applicability of the model.

339 differentially glycolytic-related genes were enriched in REACTOME_GLYCOLYSIS, GLYCOLYTIC_PROCESS, HALLMARK_GLYCOLYSIS, and other pathways. We obtained 9 key prognostic genes and constructed the prognostic evaluation model. The 3-year AUC values of the ROC curve display model are greater than 0.75, which indicates that the accuracy of the model is good. The relation of age and risk score to prognosis is shown by univariate and multivariate Cox analysis. The expression of SRD5A3, MDH2, and B3GAT3 genes was significantly upregulated in the tumor tissues, while the HDAC4 and G6PC2 genes were downregulated. The mutation rate of MDH2 and HDAC4 genes was the highest. This model could effectively distinguish the risk of poor prognosis of patients in any age stage.

The prognostic assessment models based on glycolysis-related nine-gene signature could accurately predict the prognosis of patients with GBM.

The aim was to investigate the independent prognostic factors and construct a prognostic risk prediction model to facilitate the formulation of oral squamous cell carcinoma (OSCC) clinical treatment plan. We constructed a prognostic model using univariate COX, Lasso, and multivariate COX regression analysis and conducted statistical analysis. In this study, 195 randomly obtained sample sets were defined as training set, while 390 samples constituted validation set for testing. A prognostic model was constructed using regression analysis based on nine survival-associated metabolic genes, among which PIP5K1B, NAGK, and HADHB significantly down-regulated, while MINPP1, PYGL, AGPAT4, ENTPD1, CA12, and CA9 significantly up-regulated. Statistical analysis used to evaluate the prognostic model showed a significant different between the high and low risk groups and a poor prognosis in the high risk group (P < 0.05) based on the training set. To further clarify, validation sets showed a significant difference between the high-risk group with a worse prognosis and the low-risk group (P < 0.05). Independent prognostic analysis based on the training set and validation set indicated that the risk score was superior as an independent prognostic factor compared to other clinical characteristics. We conducted Gene Set Enrichment Analysis (GSEA) among high-risk and low-risk patients to identify metabolism-related biological pathways. Finally, nomogram incorporating some clinical characteristics and risk score was constructed to predict 1-, 2-, and 3-year survival rates (C-index = 0.7). The proposed nine metabolic gene prognostic model may contribute to a more accurate and individualized prediction for the prognosis of newly diagnosed OSCC patients, and provide advice for clinical treatment and follow-up observations.

• metabolic gene
• oral squamous cell carcinoma
• prediction model
• prognostic model
• risk score

• colorectal cancer
• fatty acid metabolism
• immune
• prognosis

• acute myeloid leukemia
• bioinformatic analysis
• metabolism
• prognosis
• survival

Energy metabolic processes play important roles for tumor malignancy, indicating that related protein-coding genes and regulatory upstream genes (such as long noncoding RNAs (lncRNAs)) may represent potential biomarkers for prognostic prediction. This study will develop a new energy metabolism-related lncRNA-mRNA prognostic signature for lower-grade glioma (LGG) patients. A GSE4290 dataset obtained from Gene Expression Omnibus was used for screening the differentially expressed genes (DEGs) and lncRNAs (DELs). The Cancer Genome Atlas (TCGA) dataset was used as the prognosis training set, while the Chinese Glioma Genome Atlas (CGGA) was for the validation set. Energy metabolism-related genes were collected from the Molecular Signatures Database (MsigDB), and a coexpression network was established between energy metabolism-related DEGs and DELs to identify energy metabolism-related DELs. Least absolute shrinkage and selection operator (LASSO) analysis was performed to filter the prognostic signature which underwent survival analysis and nomogram construction. A total of 1613 DEGs and 37 DELs were identified between LGG and normal brain tissues. One hundred and ten DEGs were overlapped with energy metabolism-related genes. Twenty-seven DELs could coexpress with 67 metabolism-related DEGs. LASSO regression analysis showed that 9 genes in the coexpression network were the optimal signature and used to construct the risk score. Kaplan-Meier curve analysis showed that patients with a high risk score had significantly worse OS than those with a low risk score (TCGA: HR = 3.192, 95%CI = 2.182‐4.670; CGGA: HR = 1.922, 95%CI = 1.431‐2.583). The predictive accuracy of the risk score was also high according to the AUC of the ROC curve (TCGA: 0.827; CGGA: 0.806). Multivariate Cox regression analyses revealed age, IDH1 mutation, and risk score as independent prognostic factors, and thus, a prognostic nomogram was established based on these three variables. The excellent prognostic performance of the nomogram was confirmed by calibration and discrimination analyses. In conclusion, our findings provided a new biomarker for the stratification of LGG patients with poor prognosis.