ArticleInternational journal of surgery (London, England)2025
Sex disparity of liver cancer recurrence following surgery: sex-determining region Y gene promotes immunosuppressive microenvironment and favors metastasis.
Article in International journal of surgery (London, England), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Sex Differences in Mortality Among Patients With Hepatocellular Carcinoma.JAMA network open · 2026Article
- Sexual dimorphism in liver cancer recurrence: the role of SRY and ischemia-reperfusion injury.Hepatobiliary surgery and nutrition · 2026Article
- Sex disparity in liver cancer recurrence-from bench to bedside.Hepatobiliary surgery and nutrition · 2026Article
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17 authors.
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Abstract
backgroundMale sex is a risk factor of the development and prognosis of primary liver cancers. However, sex difference of tumor recurrence following curative resection and the underlying mechanism need to be clarified.
methodsSex and outcomes among patients undergoing resection for hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC) were investigated in two international multi-institutional databases. Murine model of postoperative HCC recurrence was used following hepatic ischemia-reperfusion (I/R) injury to mimic surgical injury in hepatocyte-specific sex-determining region Y gene (SRY) knock-in (KI) and knockout (KO) mice, as well as wildtypes (WTs).
resultsMen had a significantly worse recurrence-free survival (RFS) following curative resection of HCC or ICC versus women (5-year RFS: HCC, men 30.0% vs. women 43.9%, P = 0.041; ICC, men 18.7% vs. women 26.8%, P = 0.006, respectively) in the matched cohort. Male mice consistently developed larger recurrent tumor versus females after hepatic I/R injury, accompanied by increased polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) and decreased CD8 + T cells. Of note, SRY KI in both male and female mice increased, whereas SRY KO decreased tumor recurrence upon I/R injury. Moreover, SRY was associated with increased immunosuppressive PMN-MDSCs and decreased CD8 + T cells in both patient and murine livers after I/R injury. Mechanistically, hepatocyte SRY recruited PMN-MDSCs to the liver microenvironment following I/R injury through NF-κB-dependent CXCL1 secretion.
conclusionsMen are more likely to recur than women after liver resection of liver cancers. SRY promotes immunosuppressive microenvironment in the liver and accounts for male susceptibility of liver cancer recurrence. Targeting SRY-NFκB-CXCL1 axis may have potential value in male-specific surveillance and immunomodulatory therapy of primary liver cancer.
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