DOI: 10.1002/cam4.72185 ISSN: 2045-7634

High Expression of SSEA3 and Globo H Predicts Poor Outcomes in Resected Extrahepatic Cholangiocarcinoma: A Single‐Center Retrospective Cohort Study

Tsai‐Hsien Hung, Jung‐Tung Hung, Chun‐Nan Yeh, Rodney Cheng‐En Hsieh, Sheng‐Chi Hsu, Alice L. Yu, Yenlin Huang

ABSTRACT

Background

SSEA3, SSEA4, and Globo H glycosphingolipids have been implicated in tumor progression and immune modulation across various malignancies. However, their clinical significance in extrahepatic cholangiocarcinoma (eCCA) remains largely undefined. This study aimed to evaluate the expression levels and prognostic relevance of SSEA3, SSEA4, and Globo H in patients with eCCA.

Methods

Immunohistochemical staining for SSEA3, SSEA4, and Globo H was performed on formalin‐fixed, paraffin‐embedded tumor samples from 175 patients with resected eCCA. Expression levels were quantified using H‐scores, and optimal cut‐off values determined from receiver operating characteristic curve analysis defined high and low expression groups. Kaplan–Meier analysis with log‐rank test was used to evaluate relapse‐free survival (RFS) and overall survival (OS), and Cox regression analysis identified independent prognostic factors.

Results

Elevated expression of SSEA4 and Globo H was significantly associated with late stage of eCCA. Kaplan–Meier analysis revealed that high expression of all three glycans was significantly correlated with shorter RFS (all p  < 0.001). Similar results were observed in patients with early stage. In multivariate Cox regression analysis, high expression of SSEA3 (HR = 2.77, 95% CI: 1.03–7.46, p  = 0.044) and Globo H (HR = 2.88, 95% CI: 1.05–7.94, p  = 0.040) independently predicted poor RFS.

Conclusion

SSEA3 and Globo H independently predict RFS. These findings support the potential prognostic relevance of Globo H and SSEA3 in eCCA; however, external validation and functional studies are required before clinical implementation or therapeutic translation.

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