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pmid:34139453
Molecular subtypes based on CNVs related gene signatures identify candidate prognostic biomarkers in lung adenocarcinoma.
Baihui Li · Ziqi Huang · Wenwen Yu · Shaochuan Liu · Jian Zhang · Qingqing Wang · Lei Wu · Fan Kou · Lili Yang
Neoplasia (New York, N.Y.) · 2021 doi:10.1016/j.neo.2021.05.006
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Complete file
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With the rapid development of high-throughput DNA sequencing technologies, genomic changes have been discovered. These sequencing data provide unprecedented opportunities for identifying cancer molecular subtypes. In this article, we classified LUAD into two distinct molecular subtypes (Cluster 1 and Cluster 2) based on Copy Number Variations (CNVs) and mRNA expression data from the Cancer Genome Atlas (TCGA) based on non-negative matrix factorization. Patients in Cluster 1 had worse outcomes than that in Cluster 2. Molecular features in subtypes were assessed to explain this phenomenon by analyzing differential expression genes expression pattern, which involved in cellular processes and environmental information processing. Analysis of immune cell populations suggested different distributions of CD4+ T cells, CD8+ T cells, and dendritic cells in the two subtypes. Subsequently, two novel genes, TROAP and RASGRF1, were discovered to be prognostic biomarkers in TCGA, which were confirmed in GSE31210 and Tianjin Medical University Cancer Institute and Hospital LUAD cohorts. We further proved their crucial roles in cancers by vitro experiments. TROAP mediates tumor cell proliferation, cycle, invasion, and migration, not apoptosis. RASGRF1 has a significant effect on tumor microenvironment. 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RASGRF1 has a significant effect on tumor m"], "order_basis": "paper_text_order:1495", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["terials and methods Tumor Tissue Samples and Immunohistochemistry All samples were obtained from TMUCIH, which", "na) and DAB kit (ZLI-9019, ZSGB-BIO, China). Immunostaining was evaluated under light microscopy at 400X", "opy at 400X magnification. RASGRF1 and TROAP IHC staining were assessed by two pathologists u"], "order_basis": "paper_text_order:1804", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_imaging", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["a). Immunostaining was evaluated under light microscopy at 400X magnification. RASGRF1 and TROAP IHC"], "order_basis": "paper_text_order:2636", "id": "assay:3"}, {"role": "data_generation", "definition_id": "transfection", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ons are listed in Table S3. Cell culture and transfection BEAS-2B, A549, and NCI-H1299 cell lines were", "he indicated media as instructed. Cells were transfected by small interfering RNA (siRNA) specificall", "or RASGRF1 plasmid using Lipofectamine 3000 transfection reagent (Invitrogen, USA). The sequences of", "s were transfected by small interfering RNA (siRNA) specifically targeted TROAP using Lipofecta"], "order_basis": "paper_text_order:2981", "id": "assay:4"}, {"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": ["f Medical Science (Shanghai, China). All the cell lines were cultured in the indicated media as instructed. Cells", "e (Shanghai, China). All the cell lines were cultured in the indicated media as instructed. Cells wer", "e S3. Cell culture and transfection BEAS-2B, A549, and NCI-H1299 cell lines were purchased fro"], "order_basis": "paper_text_order:3003", "id": "assay:5"}]}