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pmid:36727080
Identification and validation of a novel angiogenesis-related gene signature for predicting prognosis in gastric adenocarcinoma.
Peipei Xu · Sailiang Liu · Shu Song · Xiang Yao · Xuechuan Li · Jie Zhang · Yinbing Liu · Ye Zheng · Ganglong Gao · Jingjing Xu
Frontiers in oncology · 2022 doi:10.3389/fonc.2022.965102
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Experiment
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Complete file
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We aimed to develop a novel lncRNA gene signature by identifying angiogenesis-related genes to better predict prognosis in STAD patients.\nMethods: The expression profiles of angiogenesis-related mRNA and lncRNA genes were collected from The Cancer Genome Atlas (TCGA). Then, the \"limma\" package was used to identify differentially expressed genes (DEGs). The expression profiles of angiogenesis-related genes were clustered by consumusclusterplus. The Pearson correlation coefficient was further used to identify lncRNAs coexpressed with angiogenesis-related clustere genes. We used Lasso Cox regression analysis to construct the angiogenesis-related lncRNAs signature. Furthermore, the diagnostic accuracy of the prognostic risk signature were validated by the TCGA training set, internal test sets and external test set. We used multifactor Cox analysis to determine that the risk score is an independent prognostic factor different from clinical characteristics. Nomogram has been used to quantitatively determine personal risk in a clinical environment. The ssGSEA method or GSE176307 data were used to evaluate the infiltration state of immune cells or predictive ability for the benefit of immunotherapy by angiogenesis-related lncRNAs signature. Finally, the expression and function of these signature genes were explored by RT-PCR and colony formation assays.\nResults: Among angiogenesis-related genes clusters, the stable number of clusters was 2. A total of 289 DEGs were identified and 116 lncRNAs were screened to have a significant coexpression relationship with angiogenic DEGs (P value<0.001 and |R| >0.5). A six-gene signature comprising LINC01579, LINC01094, RP11.497E19.1, AC093850.2, RP11.613D13.8, and RP11.384P7.7 was constructed by Lasso Cox regression analysis. The multifactor Cox analysis and Nomogram results showed that our angiogenesis-related lncRNAs signature has good predictive ability for some different clinical factors. For immune, angiogenesis-related lncRNAs signature had the ability to efficiently predict infiltration state of 23 immune cells and immunotherapy. The qPCR analysis showed that the expression levels of the six lncRNA signature genes were all higher in gastric adenocarcinoma tissues than in adjacent tissues. The functional experiment results indicated that downregulation of the expression of these six lncRNA signature genes suppressed the proliferation of ASG and MKN45 cells.\nConclusion: Six angiogenesis-related genes were identified and integrated into a novel risk signature that can effectively assess prognosis and provide potential therapeutic targets for STAD patients.", "claims": [{"id": "claim-method", "statement": "We used Lasso Cox regression analysis to construct the angiogenesis-related lncRNAs signature.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36727080", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "We used Lasso Cox regression analysis to construct the angiogenesis-related lncRNAs signature."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/ Supplementary Material . 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The results showed that the knockdown of these lncRNAs significantly inhibited the", "cRNAs in STAD by q-PCR; (B)The efficiency of knockdown of six angiogenesis-related lncRNAs in AGS c"], "order_basis": "paper_text_order:2880", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["Medicine, Shanghai Jiao Tong University. The cell lines were cultured in DMEM supplemented with 10% fetal bovine s", "ai Jiao Tong University. The cell lines were cultured in DMEM supplemented with 10% fetal bovine seru"], "order_basis": "paper_text_order:3082", "id": "assay:3"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["as shown in Figures 13D, E . Meanwhile, the CCK8 assay was applied to detect cell proliferati", "ix angiogenesis-related lncRNAs knockdown on CCK8 assay.Click here for additional data file. 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