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pmid:35419359
SLC1A5 Prefers to Play as an Accomplice Rather Than an Opponent in Pancreatic Adenocarcinoma.
Fangshi Xu · Hai Wang · Honghong Pei · Zhengliang Zhang · Liangliang Liu · Long Tang · Shuang Wang · Bin-Cheng Ren
Frontiers in cell and developmental biology · 2022 doi:10.3389/fcell.2022.800925
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Complete file
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Methods: SLC1A5's expression and somatic mutation information were determined by TCGA, GEO, Oncomine, and cBioPortal databases. Its prognostic value was assessed in TCGA cohort and was validated in three independent cohorts. The effects of SLC1A5 on the tumor immune microenvironment were analyzed by the CIBERSORT algorithm, ssGSEA method, and TISIDB and TIMER databases. The \"oncoPredict\" R package, TIDE algorithm, ImmuCellAI online tool, and GSE35141 and GSE59357 datasets were used to ascertain its therapeutic correlations. GSEA and Western blot were applied to reveal the effects of SLC1A5 on the mTORC1 signaling pathway and ferroptosis process. The biofunctions of SLC1A5 were assessed by MTT, wound-healing, Transwell, and xenograft assays. Results: SLC1A5 was significantly upregulated in the PAAD samples but was not commonly accompanied with somatic mutation (2.3%). Overexpression of SLC1A5 led to a poor prognosis and was identified as an independent prognostic factor. Moreover, high SLC1A5 expression suppressed the antitumor immune process by changing the infiltrating levels of immune cells. As for therapeutic correlations, SLC1A5 was related to the efficacy of dasatinib, sunitinib, sorafenib, and imatinib but may not predict that of radiotherapy, chemotherapeutic drugs, and immune checkpoints inhibitors (ICIs). Notably, the overexpression of SLC1A5 could activate the mTORC1 signaling pathway and may increase the cellular sensitivity to ferroptosis. Finally, the overexpression of SLC1A5 markedly promoted proliferation, migration, and invasion of pancreatic cancer cells. At the in vivo level, SLC1A5 deletion inhibited tumor growth in a mice xenograft model. Conclusions: SLC1A5 prefers to play as an accomplice rather than an opponent in PAAD. Our findings provide novel insights into PAAD treatment.", "claims": [{"id": "claim-method", "statement": "Through univariate and multivariate cox analyses, SLC1A5 (HR = 2.109, p = 0.015) and N stage (HR = 1.957, p = 0.02) were identified as the independent prognostic factors of PAAD (Figures 3F,G).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35419359", "locator": "sections[20] \"3.3 SLC1A5 Is a Critical Complement to the PAAD Prognostic Assessment\" paragraph 2", "quote": "Through univariate and multivariate cox analyses, SLC1A5 (HR = 2.109, p = 0.015) and N stage (HR = 1.957, p = 0.02) were identified as the independent prognostic factors of PAAD (Figures 3F,G)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35419359", "locator": "sections[30] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "SLC1A5 overexpression was associated with poor prognosis in pancreatic adenocarcinoma and was identified as an independent prognostic factor.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35419359", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Overexpression of SLC1A5 led to a poor prognosis and was identified as an independent prognostic factor."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "SLC1A5 overexpression was associated with poor prognosis in pancreatic adenocarcinoma and was identified as an independent prognostic factor.", "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:35419359"], "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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GSEA and Western blot were applied to reveal the effects of SLC1A5"], "order_basis": "paper_text_order:759", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["The biofunctions of SLC1A5 were assessed by MTT, wound-healing, Transwell, and xenograft ass"], "order_basis": "paper_text_order:919", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["invasion of pancreatic cancer cells. At the in vivo level, SLC1A5 deletion inhibited tumor growt"], "order_basis": "paper_text_order:1827", "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": ["2 Materials and Methods 2.8 Cell Culture and Transfection Two human pancreatic cancer cell lines (PANC", "ciency was tested by RT-qPCR after 72 h post-transfection. Supplementary Material The Supplementary Ma", "tions were 37°C with 5% CO2. SLC1A5-specific shRNA and amplification plasmids were designed by"], "order_basis": "paper_text_order:2095", "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": ["Technology (Wuhan, China). PANC-1 cells were cultured in DMEM (Dulbecco’s Modified Eagle Medium) cont", ") (Procell, Wuhan, China). SW1990 cells were cultured in Leibovitz’s L-15 medium containing 10% FBS a", "(Procell, Wuhan, China). HPDE6-C7 cells were cultured in DMEM (Dulbecco’s Modified Eagle Medium) cont"], "order_basis": "paper_text_order:2313", "id": "assay:5"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["s. The interference efficiency was tested by RT-qPCR after 72 h post-transfection. Supplementary", "The interference efficiency was tested by RT-qPCR after 72 h post-transfection. Supplementary"], "order_basis": "paper_text_order:3013", "id": "assay:6"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Through univariate and multivariate cox analyses, SLC1A5 (HR = 2.109, p = 0.015) and N stage (HR = 1.957, p = 0.02) were identified as the independent prognostic factors of PAAD (Figures 3F,G)."], "order_basis": "consumes_earlier_output", "id": "assay:7"}]}