The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36552870", "kind": "science-record", "revision": 4, "content_hash": "sha256:19468096ee5dfe51f1d71f7168364c3f8bf5160f7e2a4ecbc46e3532bea8c97a", "created_at": "2026-11-01T19:01:05Z", "updated_at": "2026-11-01T22:50:54Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "The Role of Amino Acid Metabolism of Tumor Associated Macrophages in the Development of Colorectal Cancer.", "doi": "10.3390/cells11244106", "pmid": "36552870", "authors": ["Manman Jiang", "Hongquan Cui", "Zhihong Liu", "Xin Zhou", "Ling Zhang", "Longnv Cao", "Miao Wang"], "journal": "Cells", "year": 2022, "abstract": "Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). Previous studies have shown that TAMs play a dual role in the development of colorectal cancer and promote the additional exploration of the immune escape of colorectal cancer. Studies have confirmed that macrophages utilize amino acid metabolism under the stimulation of some factors released by tumor cells, thus affecting the direction of polarization. Therefore, we investigated the effect of amino acid metabolism on macrophage function and the involved mechanism. Based on the comprehensive analysis of the GSE18804 GEO dataset and amino acid metabolism pathway, we identified the eight key enzymes of amino acid metabolism in colon TAMs, namely, ACADM, ACADS, GPX4, GSR, HADH, HMGCL, HMGCS1 and IDH1. We then evaluated the expression, survival analysis and relationship of clinicopathological features with these eight key enzymes. The results supported the critical role of these eight genes in colorectal cancer. Macrophages phagocytose tumor cells, and these eight key enzymes were identified in combination with GPX4, a critical protein of ferroptosis, suggesting that the change in the expression of these eight key enzymes in TAMs may be involved in the regulation of colorectal cancer through cell death. Correlation analysis of three programmed cell death (PCD) marker genes indicated that these eight key enzymes may cause macrophage death through pyroptosis, leading to immune escape of colorectal cancer. We also investigated the regulation of ACADS in CRC using flow cytometry, qPCR and ELISAs, which demonstrated that an ACADS deficiency polarizes TAMs to M2 macrophages. In summary, the present study revealed the relationship between amino acid metabolism and the cell death of macrophages, providing a new research direction for the molecular mechanism of macrophage polarization.", "claims": [{"id": "claim-method", "statement": "The statistical methods to assess the prognostic impact of genes in all survival analyses were performed in COAD using the “Overall Survival” function.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36552870", "locator": "sections[5] \"2.3. Identification of Key Enzymes for Amino Acid Metabolism in Colon TAMs\" paragraph 2", "quote": "The statistical methods to assess the prognostic impact of genes in all survival analyses were performed in COAD using the “Overall Survival” function."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36552870", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "The data used in the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Sixteen overlapping TAM-associated and amino acid-metabolism-related genes were identified, of which eight were associated with better colorectal cancer prognosis: ACADM, ACADS, GPX4, GSR, HADH, HMGCL, HMGCS1 and IDH1.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Consequently, we retrieved the survival analysis data of these 16 genes in GEPIA2, and the elevated expression level of 8 genes led to a better prognosis for colorectal cancer patients: ACADM, ACADS, GPX4, GSR, HADH, HMGCL, HMGCS1 and IDH1 (p < 0.05) (Figure 1D)."}, "evidence": [{"asset": "source:pmid:36552870", "locator": "sections[15] \"3.1. 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