Abstract

Background: Esophageal squamous cell cancer (ESCC) was a disease with a male predominance. Accordingly, the applicability of prognostic indicators values previously set for the general population with ESCC have not been reported for determining physical state in female. Methods: A total of 2660 patients with ESCC were pooled in this study. We analyzed clinicopathologic features and clinical prognostic predictors to determine the associations with outcome by sex. We also evaluated the relationship between total cholesterol and overall survival (OS) and further assessed the influence of total cholesterol on OS was affected by other clinicopathologic variables in female cohort. We explore the interacting with gender-specific genes and TC in ESCC by bioinformatics analysis. Findings: Compared with male, female has better overall survival (log-rank P < 0.001; HR, 0.59; 95% CI, 0.51-0.67). In addition, the results confirmed that survival outcome was significantly deteriorated in male patients with low TC level (log-rank P < 0.001; HR, 1.20; 95% CI, 1.03-1.39). Interestingly, our findings, which were based on a female population, suggested a protective role of low TC level in ESCC. In accordance with the gene expression profiles from The Cancer Genome Atlas (TCGA), differential expression genes analysis shown 20 significant differential expression genes were associated with cholesterol metabolism. Subsequently, Gene ontology (GO) analysis shown these genes were mainly enriched in cholesterol transport etc. Interpretation: In our study, we suggest patients with ESCC may benefit from targeted treatments after adjusting TC concentrations based on sex-stratified, in addition to routine cancer therapies. Funding Information: Sichuan Cancer Hospital and Institution of China. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This was a retrospective clinical study and approved by Sichuan Cancer Hospital (SCCHEC-02-2020-015).

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