LCP1 is a prognostic biomarker correlated with immune infiltrates in gastric cancer

Zeng, Qingwen; Li, Leyan; Feng, Zongfeng; Luo, Lianghua; Xiong, Jianbo; Jie, Zhigang; Cao, Yi; Li, Zhengrong

doi:10.3233/cbm-200006

Cited by 14 publications

(13 citation statements)

References 48 publications

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“…Ge et al [ 42 ] discovered that LCP1 promotes osteosarcoma progression via the activation of the JAK2/STAT3 signaling pathway. Zeng et al [ 43 ] reported that several immune marker sets were highly correlated with LCP1, which was associated with tumor-infiltrating lymphocytes in gastric cancer. In macrophages, LCP1 is required for podosome formation and function [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Immune-associated biomarkers identification for diagnosing carotid plaque progression with uremia through systematical bioinformatics and machine learning analysis

et al. 2023

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Background Uremia is one of the most challenging problems in medicine and an increasing public health issue worldwide. Patients with uremia suffer from accelerated atherosclerosis, and atherosclerosis progression may trigger plaque instability and clinical events. As a result, cardiovascular and cerebrovascular complications are more likely to occur. This study aimed to identify diagnostic biomarkers in uremic patients with unstable carotid plaques (USCPs). Methods Four microarray datasets (GSE37171, GSE41571, GSE163154, and GSE28829) were downloaded from the NCBI Gene Expression Omnibus database. The Limma package was used to identify differentially expressed genes (DEGs) in uremia and USCP. Weighted gene co-expression network analysis (WGCNA) was used to determine the respective significant module genes associated with uremia and USCP. Moreover, a protein–protein interaction (PPI) network and three machine learning algorithms were applied to detect potential diagnostic genes. Subsequently, a nomogram and a receiver operating characteristic curve (ROC) were plotted to diagnose USCP with uremia. Finally, immune cell infiltrations were further analyzed. Results Using the Limma package and WGCNA, the intersection of 2795 uremia-related DEGs and 1127 USCP-related DEGs yielded 99 uremia-related DEGs in USCP. 20 genes were selected as candidate hub genes via PPI network construction. Based on the intersection of genes from the three machine learning algorithms, three hub genes (FGR, LCP1, and C5AR1) were identified and used to establish a nomogram that displayed a high diagnostic performance (AUC: 0.989, 95% CI 0.971–1.000). Dysregulated immune cell infiltrations were observed in USCP, showing positive correlations with the three hub genes. Conclusion The current study systematically identified three candidate hub genes (FGR, LCP1, and C5AR1) and established a nomogram to assist in diagnosing USCP with uremia using various bioinformatic analyses and machine learning algorithms. Herein, the findings provide a foothold for future studies on potential diagnostic candidate genes for USCP in uremic patients. Additionally, immune cell infiltration analysis revealed that the dysregulated immune cell proportions were identified, and macrophages could have a critical role in USCP pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Immune-associated biomarkers identification for diagnosing carotid plaque progression with uremia through systematical bioinformatics and machine learning analysis

et al. 2023

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“…Its hub genes including LCP1, ACAP1, CCL19, CD3E, HLA-DRA, C1QA and CORO1A, were strongly associated with activities of immune cells. LCP1 was related to tumor infiltrating lymphocytes and plays an important role in lymphocyte formation and anti-cancer immune response [ 16 ]. The high expression of ACAP1 is positively associated with a variety of immune-related biological processes and pathways, such as adaptive immune response, T cell activation, and macrophage activation [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Distinct molecular subtypes of papillary thyroid carcinoma and gene signature with diagnostic capability

et al. 2022

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Papillary thyroid carcinoma (PTC) is heterogeneous and its molecular characteristics remain elusive. We integrated transcriptomic sequencing, genomic analysis and clinicopathologic information from 582 tissue samples of 216 PTC and 75 benign thyroid nodule (BTN) patients. We discovered four subtypes of PTC including Immune-enriched Subtype, BRAF-enriched Subtype, Stromal Subtype and CNV-enriched Subtype. Molecular subtypes were validated in an external cohort of 497 PTC cases from the TCGA. Tumors in the Immune-enriched Subtype showed higher immune infiltration and overexpression of immune checkpoints, whilst BRAF-enriched Subtype showed a higher tendency for extrathyroidal extension and more advanced TNM stage. Key oncogenes including LRRK2, SLC34A2, MUC1, FOXQ1 and KRT19 were overexpressed and enriched in oncogenic MAPK and PI3K/AKT signaling pathways in BRAF-enriched subtype. Further analysis of BRAF-enriched Subtype identified three subclasses with different degrees of malignancies. We also uncovered the molecular link of the initiation and progression from BTN to subtypes of PTC using trajectory analysis. Moreover, a 20-gene expression signature was generated for differential diagnosis of PTC from BTN patients. Together, our work identified previously unreported molecular subtypes of PTC, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping.

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“…Lymphocyte cytosolic protein 1 (LCP1) is L-plastin or leukocyte-specific plastin (17) targeted by lncRNA Maclpil (12). LCP1 plays a curtail role in immune responses by regulating cell adhesion, migration, and activation (12,18,19). LCP1 also affects cell fate.…”

Section: Discussionmentioning

confidence: 99%

Systemically Silencing Long Non-coding RNAs Maclpil With Short Interfering RNA Nanoparticles Alleviates Experimental Ischemic Stroke by Promoting Macrophage Apoptosis and Anti-inflammatory Activation

Wang

Liu

Chen

et al. 2022

Front. Cardiovasc. Med.

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BackgroundMaclpil is a proinflammatory long non-coding RNA highly expressed on monocyte-derived macrophages in the ischemic brain. This study investigated the impact and the mechanisms of systemically delivering nanoparticle Maclpil short interfering RNA (siRNA) on experimental ischemic stroke in a mouse model.MethodsIschemic stroke (focal cerebral ischemia) was induced in male C57BL/6 mice through the middle cerebral artery occlusion. Three hours thereafter, mice were intravenously injected with Maclpil siRNA or scramble siRNA nanoparticles. Bone marrow cell-derived macrophages were transfected with Maclpil or scramble siRNA and subjected to oxygen glucose deprivation culture. The influence of silencing Maclpil on stroke outcomes, neuroinflammation, and macrophage fates was assessed via histology, flow cytometry, Western blotting, and quantitative PCR analysis.ResultsThree days following stroke induction, siRNA silencing Maclpil substantially reduced ischemic infarction size and improved neurological behaviors. Silencing Maclpil also markedly attenuated the accumulation of monocyte-derived macrophages, CD4+ T cells, and CD8+ T cells in the ischemic hemisphere without affecting microglia cellularity. Reciprocally, myeloid cells and both subsets of T cells were elevated in mouse peripheral blood following Maclpil siRNA treatment. Under oxygen glucose deprivation conditions that mimicked hypoxia and hypoglycemia in vitro, Maclpil siRNA silencing augmented macrophage apoptosis in conjunction with upregulation of proapoptotic Bax and caspase 3 expressions. siRNA knocking down Maclpil skewed macrophages from proinflammatory classical toward anti-inflammatory alternative activation as evidenced by increased arginase 1, Ym1, and Fizz1 and reduced inducible nitric oxide synthase, IL-1β, and TNF-α mRNA levels. Consistent with macrophage phenotype switching, silencing Maclpil by siRNA enhanced fatty acid oxidation as indicated by increased mRNA levels of 3 key metabolic enzymes (ACADM, ACADVL, and HADHA).ConclusionSystemically silencing Maclpil by siRNA nanoparticles attenuated experimental ischemic stroke by promoting macrophage apoptosis and anti-inflammatory alternative activation. Identifying and targeting Maclpil human homolog(s) may help develop a novel therapy for stroke clinical management.

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LCP1 is a prognostic biomarker correlated with immune infiltrates in gastric cancer

Cited by 14 publications

References 48 publications

Immune-associated biomarkers identification for diagnosing carotid plaque progression with uremia through systematical bioinformatics and machine learning analysis

Immune-associated biomarkers identification for diagnosing carotid plaque progression with uremia through systematical bioinformatics and machine learning analysis

Distinct molecular subtypes of papillary thyroid carcinoma and gene signature with diagnostic capability

Systemically Silencing Long Non-coding RNAs Maclpil With Short Interfering RNA Nanoparticles Alleviates Experimental Ischemic Stroke by Promoting Macrophage Apoptosis and Anti-inflammatory Activation

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