A Prognostic Model for Colon Adenocarcinoma Patients Based on Ten Amino Acid Metabolism Related Genes

Ren, Yangzi; He, Shangwen; Feng, Siyang; Yang, Wei

doi:10.3389/fpubh.2022.916364

Cited by 7 publications

(5 citation statements)

References 46 publications

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“…The human ribosomal protein RPS17 plays an important role in several diseases. The mutations in the ribosomal protein S17 (RPS17) gene are closely associated with hereditary bone marrow failure syndrome 47 , while it has also been shown that RPS17 may affect CRC prognosis by controlling amino acid metabolism 48 , which is consistent with our study. The heat shock protein family A member 1A (HSPA1A) belongs to the heat shock protein 70 family.…”

Section: Discussionsupporting

confidence: 91%

Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer

Xü

Zhang

Lin

et al. 2023

Sci Rep

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Ferroptosis is an iron-dependent form of cell death induced by lipid oxidation with an essential role in diseases, including cancer. Since prognostic value of ferroptosis-dependent related genes (FDRGs) in colorectal cancer (CRC) remains unclear, we explored the significance of FDRGs in CRC through comprehensive single-cell analysis. We downloaded the GSE161277 dataset for single-cell analyses and calculated the ferroptosis-dependent gene score (FerrScore) for each cell type. According to each cell type-specific median FerrScore, we categorized the cells into low- and high-ferroptosis groups. By analyzing differentially-expressed genes across the two groups, we identified FDRGs. We further screened these prognosis-related genes used to develop a prognostic signature and calculated its correlation with immune infiltration. We also compared immune checkpoint gene efficacy among different risk groups, and qRT-PCR was performed in colorectal normal and cancer cell lines to explore whether the signature genes could be used as clinical prognostic indicators. In total, 523 FDRGs were identified. A prognostic signature including five signature genes was constructed, and patients were divided into two risk groups. The high-risk group had poor survival rates and displayed high levels of immune infiltration. Our newly developed ferroptosis-based prognostic signature possessed a high predictive ability for CRC.

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Section: Discussionsupporting

confidence: 91%

Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer

Xü

Zhang

Lin

et al. 2023

Sci Rep

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“…The nomogram also had a high C-index and accuracy. Compared with earlier research (Ren's 10-gene signature), our signature's 5-years AUC was higher than Ren's and was more concise with only five genes (Ren et al, 2022). These outcomes indicated our model was robust and performed well in predicting the survival of colorectal cancer patients.…”

Section: Discussionmentioning

confidence: 48%

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

Peng

Zheng

Guo

et al. 2022

Front. Mol. Biosci.

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Based on amino acid metabolism-related genes (AAMRGs), this study aimed at screening out key prognosis-related genes and finding the underlying correlation between the amino acid metabolism and tumor immune microenvironment of colorectal cancer. A total of 448 amino acid metabolism-related genes were obtained from MsigDB. The risk signature was built based on differential expression genes, univariate Cox, and LASSO analyses with 403 patients’ data downloaded from the TCGA database. Survival analysis and independence tests were performed to confirm the validity of the risk signature. Single-sample gene set enrichment analysis (ssGSEA), tumor mutation burden (TMB), the score of tumor immune dysfunction and exclusion (TIDE), the immunophenoscore obtained from The Cancer Immunome Atlas database, and the IC50 of drugs were used to find the relationship among the risk signature, immune status, immunotherapy response, and drug sensitivity of colorectal cancer. We identified five amino acid metabolism-related genes for the construction of the risk signature, including ENOPH1, ACAT1, ALDH4A1, FAS, and ASPG. The low-risk group was significantly associated with a better prognosis (p < 0.0001). In the entire set, the area under the curve (AUC) for 1, 3, and 5 years was 0.717, 0.734, and 0.764, respectively. We also discovered that the low-risk subgroup was related to more activity of immune cells, had higher expression of some immune checkpoints, and was more likely to benefit from immunotherapy. ssGSEA revealed that except the processes of glutamine histidine, lysine, tyrosine, and L-phenylalanine metabolism, the other amino acid metabolism pathways were more active in the samples with the low risk scores, whereas the activities of synthesis and transportation of most amino acids were similar. Hedgehog signaling, WNT/β-catenin signaling, mitotic, notch signaling, and TGF-β signaling were the top five pathways positively associated with the risk score. To sum up, AAMRGs were associated with the immune microenvironment of CRC patients and could be applied as biomarkers to predict the prognosis and immunotherapy response of patients.

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“…ANXA5, serving as a marker for macrophage subsets, could predict immune therapy responses in endometrial cancer [ 58 ]. GAMT served as one of the components to predict the sensitivity of colorectal adenocarcinoma patients to immune therapy targeting PD-1 and CTLA-4 [ 59 ]. The downregulation of SLC7A2 upregulated CXCL1 through the PI3K/Akt/NF-κB pathway, recruiting bone marrow-derived suppressor cells and exerted a tumor immune inhibitory effect [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

The macrophage-associated prognostic gene ANXA5 promotes immunotherapy resistance in gastric cancer through angiogenesis

Hong,

Wen,

Wang

et al. 2024

BMC Cancer

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Gastric cancer (GC) remains a predominant form of malignant tumor globally, necessitating innovative non-surgical therapeutic approaches. This investigation aimed to delineate the expression landscape of macrophage-associated genes in GC and to evaluate their prognostic significance and influence on immunotherapeutic responsiveness. Utilizing the CellMarker2.0 database, we identified 69 immune cell markers with prognostic relevance in GC, including 12 macrophage-specific genes. A Weighted Gene Co-Expression Network Analysis (WGCNA) isolated 3,181 genes correlated with these macrophage markers. The Cancer Genome Atlas (TCGA-STAD) dataset was employed as the training set, while data from the GSE62254 served as the validation cohort. 13 genes were shortlisted through LASSO-Cox regression to formulate a prognostic model. Multivariable Cox regression substantiated that the calculated risk score serves as an imperative independent predictor of overall survival (OS). Distinct macrophage infiltration profiles, pathway associations, treatment susceptibilities, and drug sensitivities were observed between high- and low-risk groups. The preliminary validation of ANXA5 in predicting the survival rates of GC patients at 1 year, 3 years, and 5 years, as well as its expression levels were higher and role in promoting tumor angiogenesis in GC through immunohistochemistry and angiogenesis experiments. In summary, macrophage-related genes were potentially a novel crosstalk mechanism between macrophages and endothelial cells in the tumor microenvironment, and the interplay between inflammation and angiogenesis might have also offered new therapeutic targets, providing a new avenue for personalized treatment interventions.

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A Prognostic Model for Colon Adenocarcinoma Patients Based on Ten Amino Acid Metabolism Related Genes

Cited by 7 publications

References 46 publications

Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer

Integrated single-cell and bulk RNA sequencing analysis identifies a prognostic signature related to ferroptosis dependence in colorectal cancer

Amino acid metabolism genes associated with immunotherapy responses and clinical prognosis of colorectal cancer

The macrophage-associated prognostic gene ANXA5 promotes immunotherapy resistance in gastric cancer through angiogenesis

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