CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34676245", "kind": "science-record", "revision": 4, "content_hash": "sha256:81b385a9c5dcc6c226ebaf7d5958d71f9ad32f76732c3b22cc9fb0bf2206f912", "created_at": "2026-11-01T17:36:20Z", "updated_at": "2026-11-01T22:05:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "CXCR4 is a Novel Biomarker Correlated With Malignant Transformation and Immune Infiltrates in Gastric Precancerous Lesions.", "doi": "10.3389/fmolb.2021.697993", "pmid": "34676245", "authors": ["Xiaotao Jiang", "Junhui Zheng", "Lanxing Liu", "Kailin Jiang", "Yi Wen", "Yanhua Yan", "Yufeng Liu", "Limei Zhong", "Yuancheng Huang", "Zhengyang Yao", "Kechao Nie", "Zhihua Zheng", "Jinglin Pan", "Peng Liu", "Kunhai Zhuang", "Fengbin Liu", "Shijie Xu", "Peiwu Li"], "journal": "Frontiers in molecular biosciences", "year": 2021, "abstract": "Background: As early gastric cancer (EGC) has a far better prognosis than advanced gastric cancer (GC), early diagnosis and treatment are essential. However, understanding the mechanism of the process from gastric precancerous lesion (GPL) becoming EGC has made little advances. Besides, biomarkers that can monitor the progression of GPL-to-GC are still much insufficient. Methods: Key gene modules associated with GPL progression to EGC were identified by integrating two GPL-related data sets, GSE55696 and GSE130823, using the WGCNA method. Combining with the TCGA-STAD cohort, hub genes were identified. Immunofluorescence was conducted to validate the expression. To explore the implication of hub genes in GPL malignant transformation, a correlation test was conducted to identify their co-expression genes, co-expression cytokines, and co-expression immune cells. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to shrink CXCR4-related predictors and construct a prognostic model. Functional enrichment was applied for exploring the potential mechanism. Results: The green module in GSE55696 and the yellow module in GSE130823 were regarded as key gene modules associated with GPL progression to EGC, and 219 intersection genes from them were mainly enriched in critical immune biological processes. Combining with the TCGA-STAD cohort, CXCR4 was identified as a novel biomarker correlated with the malignant transformation of GPL, the positive rate of which was increased with GPL progression according to immunofluorescence. CXCR4 co-expression genes were found mainly involved in regulation of actin. CXCR4 co-expression cytokines were enriched in regulation of chemotaxis, cell chemotaxis, mononuclear cell migration, leukocyte chemotaxis, etc. As for co-expression immune cells, the expression level of CXCR4 was positively correlated with the abundance of macrophages but negatively correlated with that of effector memory T cells and NKT cells during GPL malignant transformation. In addition, the CXCR4-related prognostic model was able to predict the prognosis of GC and serve as an independent predictor for overall survival (OS). Conclusions: CXCR4 was a novel biomarker correlated with malignant transformation of GPL and played a vital role in the control of tumor immunity. CXCR4 is possible to serve as a therapeutic target for malignant transformation of GPL.", "claims": [{"id": "claim-method", "statement": "To identify key gene modules associated with GPL progression, weighted gene co-expression analysis (WGCNA) was used to construct a co-expressed gene network and explore its correlation with clinical traits.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34676245", "locator": "sections[4] \"Identification of Key Gene Modules Associated With GPL Progression to EGC\" paragraph 2", "quote": "To identify key gene modules associated with GPL progression, weighted gene co-expression analysis (WGCNA) was used to construct a co-expressed gene network and explore its correlation with clinical traits."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available data sets were analyzed in this study. These data can be found here: TCGA and the GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34676245", "locator": "sections[27] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available data sets were analyzed in this study. These data can be found here: TCGA and the GEO database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CXCR4 expression and its immunofluorescence positive rate increased with GPL progression and were positively correlated with tumorigenesis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34676245", "locator": "sections[19] \"Identification and Validation of Novel Genes Associated With GPL Progression to EGC\" paragraph 2", "quote": "Expression profile data showed that CXCR4 expression was a significant difference among pathological stages (GSE55696: p in the one-way ANOVA test <0.0001, Figure 2B; GSE130823, p in the one-way ANOVA test = 0.0004, Figure 2D) and significantly positively correlated with tumorigenesis (GSE55696: r = 0.6157, p < 0.0001, Figure 2C; GSE130823, r = 0.5799, p = 0.0001, Figure 2E)."}, {"asset": "source:pmid:34676245", "locator": "sections[19] \"Identification and Validation of Novel Genes Associated With GPL Progression to EGC\" paragraph 2", "quote": "The positive rate of CXCR4 was also a significant difference among pathological stages (p in the one-way ANOVA test = 0.0051, Figures 3A,B) and significantly positively correlated with tumorigenesis (r = 0.7667, p = 0.0003, Figure 3C)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CXCR4 expression and its immunofluorescence positive rate increased with GPL progression and were positively correlated with tumorigenesis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:34676245"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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