Acid ceramidase expression and biomarker potential in patients with locally advanced rectal cancer.

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This study aimed to explore the clinical significance of AC gene and protein expression in rectal cancer. We analyzed the expression of ASAH1, BAX, and BCL2 through quantitative Real-Time PCR in paired tumor and non-tumor tissue samples obtained from patients with locally advanced rectal cancer (LARC) prior to neoadjuvant chemoradiotherapy. Additionally, serum AC levels and standard biochemical parameters were assessed. We further evaluated ASAH1 expression using RNA-seq data from publicly available TCGA-READ datasets accessed via the UCSC Xena Browser. Two approaches indicated a significant reduction in ASAH1 expression in tumor tissue (p=0.004 and p<0.001, respectively). Receiver operating characteristic curve analysis revealed a modest capacity for ASAH1 expression to differentiate between tumor and non-tumor tissue in LARC patients (AUC=0.652, p=0.042). No correlation was observed between ASAH1 expression and the BAX/BCL2 ratio in tumor tissue, nor with serum AC levels or the CRP-albumin-lymphocyte (CALLY) index. Conversely, serum AC levels exhibited a negative correlation with the BAX/BCL2 ratio (rs=-0.536, p=0.002, FDR-adjusted q=0.021). Furthermore, ASAH1 expression, AC levels, and the CALLY index were not linked to overall survival or treatment response. A key finding of this study is the inverse relationship between serum AC levels and the pro-apoptotic status of tumor tissue, suggesting that circulating AC may provide valuable insights into tumor apoptotic activity. Further large-scale studies are necessary to validate these preliminary findings and elucidate the biomarker potential of AC in rectal cancer.", "claims": [{"id": "claim-method", "statement": "The difference in expression between tumor and adjacent non-tumor tissues was statistically significant across the entire cohort (Wilcoxon matched-pairs signed-rank test, P ═ 0.004; Figure 1A). An independent analysis of RNA-seq data from the TCGA-READ cohort, conducted using the UCSC Xena Browser, corroborated a significant decrease in ASAH1 expression in primary tumor tissues compared to normal rectal tissues (Mann–Whitney U test, P < 0.001; Figure 1B).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41313810", "locator": "sections[9] \"Results\" paragraph 4", "quote": "The difference in expression between tumor and adjacent non-tumor tissues was statistically significant across the entire cohort (Wilcoxon matched-pairs signed-rank test, P ═ 0.004; Figure 1A). An independent analysis of RNA-seq data from the TCGA-READ cohort, conducted using the UCSC Xena Browser, corroborated a significant decrease in ASAH1 expression in primary tumor tissues compared to normal rectal tissues (Mann–Whitney U test, P < 0.001; Figure 1B)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41313810", "locator": "sections[15] \"Data Availability\" paragraph 2", "quote": "Data are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ASAH1 expression was significantly reduced in rectal tumor tissue, with P = 0.004 in paired qRT-PCR samples and P < 0.001 in the TCGA-READ RNA-seq cohort.", "kind": "quantitative", "target": {"value": 0.001, "unit": "p-value", "tolerance": null, "source": "The difference in expression between tumor and adjacent non-tumor tissues was statistically significant across the entire cohort (Wilcoxon matched-pairs signed-rank test, P ═ 0.004; Figure 1A). 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