LGR6 Acts as an Oncogene and Induces Proliferation and Migration of Gastric Cancer Cells

Yang, Juan; Fan, Meiyang; Liu, Siyuan; Zhang, Lingyu; Gao, Shanfeng; Li, Rufeng; Xiong, Xiaofan; Lin, Han; Xiao, Xuan; Zhao, Lingyu; Tong, Dongdong

doi:10.1615/critreveukaryotgeneexpr.2021041271

Cited by 5 publications

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“…LGR6 has been confirmed to be at high levels in GC cell lines and gastric adenocarcinoma tissues. Silencing LGR6 inhibits the proliferation and migration of MN45 and BGC-823 cells, and simultaneously inhibits the expression of MMP-9 , β-catenin, CCNA2 , CDK-2 , and ERK1/2 [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

Ma,

Liu,

et al. 2024

World J Gastrointest Oncol

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BACKGROUND Treatment options for patients with gastric cancer (GC) continue to improve, but the overall prognosis is poor. The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present, and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups. AIM To determined the effects of differentially expressed immune-related genes (DEIRGs) on the development, prognosis, tumor microenvironment (TME), and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations. METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas (TCGA), and immune-related genes (IRGs) were searched from ImmPort. DEIRGs were extracted from the intersection of the differentially-expressed genes (DEGs) and IRGs lists. The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes (KEGGs) and Gene Ontology (GO) databases. To identify genes associated with prognosis, a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression. The tumor risk score was divided into high- and low-risk groups. The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model. The infiltration of immune cells was obtained using ‘CIBERSORT,’ and the infiltration of immune subgroups in high- and low-risk groups was analyzed. The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed. RESULTS We collected 412 GC and 36 adjacent tissue samples, and identified 3627 DEGs and 1311 IRGs. A total of 482 DEIRGs were obtained. GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes, receptor ligand activity, and signaling receptor activators. KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors, neuroactive ligand receptor interactions, and viral protein interactions. We ultimately obtained an immune-related signature based on 10 genes, including 9 risk genes (LCN1 , LEAP2 , TMSB15A mRNA, DEFB126 , PI15 , IGHD3-16 , IGLV3-22 , CGB5 , and GLP2R ) and 1 protective gene (LGR6 ). Kaplan-Meier survival analysis, receiver operating characteristic curve analysis, and risk curves confirmed that the risk model had good predictive ability. Multivariate COX analysis showed that age, stage, and risk score were independent prognostic factors for patients with GC. Meanwhile, patients in the low-risk group had higher tumor mutation burden and immunophenotype, which can be used to predict the immune checkpoint inhibitor response. Both cytotoxic T lymphocyte antigen4+ and programmed death 1+ patients with lower risk scores were more sensitive to immunotherapy. CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME. By providing risk factor analysis and prognostic information, our risk model can provide new directions for immunotherapy in GC patients.

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Section: Discussionmentioning

confidence: 99%

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

Ma,

Liu,

et al. 2024

World J Gastrointest Oncol

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“…Chemokine receptor CXCR4, belonging to the G protein-coupled receptor (GPCR) family, impairs chemosensitivity and promotes cell migration and invasion, stemness, and tumorigenesis of GC [15][16][17]. In addition, leucine-rich repeat-containing GPCR 6 (LGR6) facilitates cell growth and migratory and invasive ability in GC through the PI3K/AKT/mTOR pathway [18,19]. Liu et al showed that Neuropilin-1 (NRP1) represses CD8+ T cell-mediated antitumor immune responses and anti-PD1 immunotherapy, leading to tumor relapse [20].…”

Section: Introductionmentioning

confidence: 99%

Comprehensive analysis of cuproptosis-related immune biomarker signature to enhance prognostic accuracy in gastric cancer

Tian

Sun

et al. 2023

Aging

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Background: Gastric cancer (GC) is a malignant tumor with high prevalence and fatality. Cuproptosis is a recently identified copper-dependent programmed cell death mechanism. Multiple studies have demonstrated the profound impact of the immune microenvironment on tumor development. Hence, we decided to excavate the potential functional roles of cuproptosis-related immune genes (CRIGs) in GC and their values as biomarkers. Methods: Cuproptosis-and immune-related genes were curated from top published studies on cell cuproptosis and cellular immunity. Transcriptome data and clinical information were obtained from TCGA, GTEx, and GEO databases. Cox and LASSO analyses were used to establish a prognostic signature for GC. Long-term prognosis, immune infiltration, immune checkpoint, and drug response were compared between signature groups. CRIG expression in GC scRNA-seq was analyzed. Immunohistochemistry was used to evaluate CRIG and cuproptosis regulator FDX1 in GC tissues. Results: Seven CRIGs (ANOS1, CTLA4, ITGAV, CXCR4, NRP1, FABP3, and LGR6) were selected to establish a potent signature to forecast the long-term prognosis of patients. GC patients had worse prognosis and poor responses to chemotherapeutic drugs (5-Fluorouracil and paclitaxel) in the high-risk group. scRNA-seq revealed that CTLA4, ITGAV, CXCR4, and NRP1 enrichment in specific cell types regulated the progression of GC. Moreover, NRP1, CXCR4, LGR6, CTLA4, and FDX1 were elevated in GC tissues, with a positive correlation between their expression and FDX1. Conclusions: To conclude, this study first provides insights into the functions of CRIGs in GC. Furthermore, a robust cuproptosis-related immune biomarker signature was established to forecast the long-term survival of GC patients accurately.

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“…Elevated LGR6 expression is correlated with poor prognosis of esophageal cancer, 20 , 21 breast cancer, 22 cervical cancer, 23 and ovarian cancer. 24 It also confers malignant phenotypes by promoting tumor proliferation and invasion in gastric cancer, 25 , 26 breast cancer, 22 and glioblastoma. 27 Furthermore, a recent study demonstrated that LGR6 is transcriptionally upregulated by overexpressed β‐catenin in cervical cancer.…”

Section: Introductionmentioning

confidence: 99%

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β‐catenin signaling in lung cancer

Sunaga,

Kaira,

Shimizu

et al. 2023

Thoracic Cancer

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BackgroundMolecular abnormalities in the Wnt/β‐catenin pathway confer malignant phenotypes in lung cancer. Previously, we identified the association of leucine‐rich repeat‐containing G protein‐coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon β‐catenin knockdown in non‐small cell lung cancer (NSCLC) cells carrying CTNNB1 mutations. The aim of this study was to explore the mechanisms underlying this association and the accompanying phenotypes.MethodsLGR6 expression in lung cancer cell lines and surgical specimens was analyzed using quantitative RT‐PCR and immunohistochemistry. Cell growth was assessed using colony formation assay. Additionally, mRNA sequencing was performed to compare the expression profiles of cells subjected to different treatments.ResultsLGR6 was overexpressed in small cell lung cancer (SCLC) and NSCLC cell lines, including the CTNNB1‐mutated NSCLC cell lines HCC15 and A427. In both cell lines, LGR6 knockdown inhibited cell growth. LGR6 expression was upregulated in spheroids compared to adherent cultures of A427 cells, suggesting that LGR6 participates in the acquisition of cancer stem cell properties. Immunohistochemical analysis of lung cancer specimens revealed that the LGR6 protein was predominantly overexpressed in SCLCs, large cell neuroendocrine carcinomas, and lung adenocarcinomas, wherein LGR6 overexpression was associated with vascular invasion, the wild‐type EGFR genotype, and an unfavorable prognosis. Integrated mRNA sequencing analysis of HCC15 and A427 cells with or without LGR6 knockdown revealed LGR6‐related pathways and genes associated with cancer development and stemness properties.ConclusionsOur findings highlight the oncogenic roles of LGR6 overexpression induced by aberrant Wnt/β‐catenin signaling in lung cancer.

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LGR6 Acts as an Oncogene and Induces Proliferation and Migration of Gastric Cancer Cells

Cited by 5 publications

References 0 publications

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

Comprehensive analysis of cuproptosis-related immune biomarker signature to enhance prognostic accuracy in gastric cancer

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/β‐catenin signaling in lung cancer

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