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pmid:37127623
Liquid-liquid phase separation throws novel insights into treatment strategies for skin cutaneous melanoma.
Jianlan Liu · Shengbin Pei · Pengpeng Zhang · Keyu Jiang · Binlin Luo · Zuoqiong Hou · Gang Yao · Jian Tang
BMC cancer · 2023 doi:10.1186/s12885-023-10847-w
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Experiment
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Complete file
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However, to date, the clinical significance of LLPS in skin cutaneous melanoma (SKCM, hereafter referred to as melanoma) remains to be elucidated. In the current study, the impact of LLPS-related genes on melanoma prognosis has been explored.\nMETHODS: LLPS-related genes were retrieved from the DrLLPS database. The prognostic feature for LLPS in melanoma was developed in The Cancer Genome Atlas (TCGA) dataset and verified in the GSE65904 cohort. Based on risk scores, melanoma patients were categorized into high- and low-risk groups. Thereafter, the differences in clinicopathological correlation, functional enrichment, immune landscape, tumor mutational burden, and impact of immunotherapy between the two groups were investigated. Finally, the role of key gene TROAP in melanoma was validated by in vitro and in vivo experiments.\nRESULTS: The LLPS-related gene signature was developed based on MLKL, PARVA, PKP1, PSME1, RNF114, and TROAP. The risk score was a crucial independent prognostic factor for melanoma and patients with high-risk scores were related to a worse prognosis. Approximately, all immune-relevant characteristics, such as immune cell infiltration and immune scores, were extremely evident in patients with low-risk scores. The findings from the in vitro and in vivo experiments indicated that the viability, proliferation, and invasion ability of melanoma cells were drastically decreased after the knockdown of TROAP.\nCONCLUSION: Our gene signature can independently predict the survival of melanoma patients. It provides a basis for the exploration of the relationship between LLPS and melanoma and can offer a fresh perspective on the clinical diagnosis and treatment of the disease.", "claims": [{"id": "claim-method", "statement": "A univariate Cox analysis of the overall survival (OS) of TCGA cohorts was implemented to filter the LLPS-related genes with a prognostic capacity of p < 0.01. 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The least absolute shrinkage and selection operator (LASSO) Cox analysis method was employed to screen the alternative genes and establish prognostic features using the “glmnet” package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37127623", "locator": "sections[42] \"notes\" paragraph 1", "quote": "The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Notably, the LLPS-related gene signature achieves the AUC values of 0.885, 0.608, and 0.724 in the training, testing set, and entire TCGA sets, respectively, suggesting a substantially effective performance for OS prediction in melanoma (Fig. 3M–O).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37127623", "locator": "sections[24] \"Evaluation of LLPS-related prognostic model based on the TCGA database\" paragraph 2", "quote": "Notably, the LLPS-related gene signature achieves the AUC values of 0.885, 0.608, and 0.724 in the training, testing set, and entire TCGA sets, respectively, suggesting a substantially effective performance for OS prediction in melanoma (Fig. 3M–O)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Notably, the LLPS-related gene signature achieves the AUC values of 0.885, 0.608, and 0.724 in the training, testing set, and entire TCGA sets, respectively, suggesting a substantially effective performance for OS prediction in melanoma (Fig. 3M–O).", "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:37127623"], "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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