Spinster Homologue 2 Expression Correlates With Improved Patient Survival in Hepatocellular Carcinoma Despite Association With Lymph-Angiogenesis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38545475", "kind": "science-record", "revision": 3, "content_hash": "sha256:75d2b78075949b25efafd9144a46729a48cd8b8ba308a8bbe3ffce8b4fcc5623", "created_at": "2026-11-01T19:20:30Z", "updated_at": "2026-11-01T22:11:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Spinster Homologue 2 Expression Correlates With Improved Patient Survival in Hepatocellular Carcinoma Despite Association With Lymph-Angiogenesis.", "doi": "10.14740/wjon1732", "pmid": "38545475", "authors": ["Joy Sarkar", "Masanori Oshi", "Vikas Satyananda", "Kohei Chida", "Li Yan", "Aparna Maiti", "Nitai Hait", "Itaru Endo", "Kazuaki Takabe"], "journal": "World journal of oncology", "year": 2024, "abstract": "Background: Spinster homologue 2 (SPNS2) is a transporter of sphingosine-1-phosphate (S1P), a bioactive lipid linked to cancer progression. We studied the link between SPNS2 gene expression, tumor aggressiveness, and outcomes in patients with hepatocellular carcinoma (HCC).\nMethods: Gene expression in patients with HCC was analyzed from the Cancer Genome Atlas (TCGA) (n = 350) and GSE76427 (n = 115) as a validation cohort, as well as liver tissue cohort GSE6764 (n = 75).\nResults: High-SPNS2 HCC was significantly associated with high level of lymph-angiogenesis-related factors. SPNS2 expression was significantly higher in normal liver and early HCC versus advanced HCC (P < 0.02). High SPNS2 levels enriched immune response-related gene sets; inflammatory, interferon (IFN)-α, IFN-γ responses, and tumor necrosis factor (TNF)-α, interleukin (IL)-6/Janus kinase/signal transducer and activator of transcription (JAK/STAT3) signaling, complement and allograft rejection, but did not significantly infiltrate specific immune cells nor cytolytic activity score. High-SPNS2 HCC enriched tumor aggravating pathway gene sets such as KRAS (Kirsten rat sarcoma virus) signaling, but inversely correlated with Nottingham histological grade, MKI67 (marker of proliferation Ki-67) expression, and cell proliferation-related gene sets. Further, high-SPNS2 HCC had significantly high infiltration of stromal cells, showing that low-SPNS2 HCC is highly proliferative. Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively).\nConclusions: Although SPNS2 expression correlated with lymph-angiogenesis and other cancer-promoting pathways, it also enriched immune response. SPNS2 levels were higher in normal liver compared to HCC, and inversely correlated with cancer cell proliferation and better survival. SPNS2 expression may be beneficial in HCC patients despite detrimental in-vitro effects.", "claims": [{"id": "claim-method", "statement": "Kaplan-Meier survival analysis was performed in R for the survival analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38545475", "locator": "sections[6] \"Statistical analysis\" paragraph 2", "quote": "Kaplan-Meier survival analysis was performed in R for the survival analysis."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data supporting the findings of this study are publicly available in TCGA and GEO and can be accessed via https://portal.gdc.cancer.gov/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38545475", "locator": "sections[19] \"Data Availability\" paragraph 2", "quote": "The data supporting the findings of this study are publicly available in TCGA and GEO and can be accessed via https://portal.gdc.cancer.gov/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "High-SPNS2 HCC had significantly high infiltration of stromal cells, showing that low-SPNS2 HCC is highly proliferative. Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively).", "kind": "quantitative", "target": {"value": 0.031, "unit": "p-value", "tolerance": null, "source": "Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively)."}, "evidence": [{"asset": "source:pmid:38545475", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "High-SPNS2 HCC had significantly high infiltration of stromal cells, showing that low-SPNS2 HCC is highly proliferative. Finally, high-SPNS2 HCC was associated with better disease-free, disease-specific, and overall survival (P = 0.031, 0.046, and 0.040, respectively).", "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:38545475"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE6764"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE6764"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38545475", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.14740/wjon1732", "sha256": 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