Background/Objectives: Cholangiocarcinoma (CCA) is an aggressive malignancy with a poor prognosis, creating an urgent need for novel biomarkers to improve risk stratification. The prognostic significance of the transmembrane glycoprotein CD44 and its isoforms (CD44s, v5, v6) in CCA remains controversial. This preliminary study aimed to investigate whether the combined loss of these isoforms could serve as a distinct prognostic indicator.Methods: We evaluated the expression of CD44s, CD44v5, and CD44v6 via immunohistochemistry on a retrospective cohort of 61 paraffin-embedded CCA patient tissue blocks from Ramathibodi Hospital, Bangkok, Thailand. Expression levels were correlated with clinicopathological parameters. Survival analyses, including Kaplan–Meier and Cox proportional hazards models, were used to determine the prognostic value of individual isoforms and the complete absence of all three.Results: Expression of CD44s, CD44v5, and CD44v6 was found in 52.5%, 47.5%, and 82.0% of tumors, respectively. In univariate and multivariate analyses, the expression of any single isoform was not a significant predictor of overall survival. However, a subgroup of 8 patients (13.1%) was identified whose tumors were negative for all three isoforms, a phenotype we termed “CD44s-v5-v6 Null”. This status was significantly associated with advanced TNM stages (p= 0.022). Patients with these Null tumors also showed a clinically relevant, though not statistically significant, trend towards poorer survival (median 7.0 vs. 12.0 months,p= 0.336).Conclusions: Individual CD44 isoforms did not serve as reliable independent prognostic markers in this cohort. Instead, the complete loss of the CD44 expression program characterizes a potential “CD44s-v5-v6 Null” phenotype associated with advanced-stage disease.
背景/目的：胆管癌是一种侵袭性强、预后差的恶性肿瘤，亟需新型生物标志物以改善风险分层。跨膜糖蛋白CD44及其亚型（CD44s、v5、v6）在胆管癌中的预后意义仍存在争议。本初步研究旨在探讨这些亚型的联合缺失是否可作为独立的预后指标。 方法：我们通过免疫组织化学方法，对来自泰国曼谷拉玛提博迪医院的61例石蜡包埋胆管癌患者组织样本进行回顾性队列研究，评估CD44s、CD44v5和CD44v6的表达情况。将表达水平与临床病理参数进行关联分析，并采用Kaplan-Meier法和Cox比例风险模型进行生存分析，以评估单个亚型及三者完全缺失的预后价值。 结果：CD44s、CD44v5和CD44v6在肿瘤中的表达率分别为52.5%、47.5%和82.0%。单因素和多因素分析显示，单个亚型的表达均非总生存期的显著预测因子。然而，我们发现8例患者（13.1%）的肿瘤中三种亚型均呈阴性，我们将此表型定义为“CD44s-v5-v6缺失型”。该状态与晚期TNM分期显著相关（p=0.022）。尽管未达到统计学显著性（p=0.336），但此类缺失型肿瘤患者显示出临床相关的生存期缩短趋势（中位生存期7.0个月 vs. 12.0个月）。 结论：在本研究队列中，单个CD44亚型不能作为可靠的独立预后标志物。相反，CD44表达程序的完全缺失构成了潜在的“CD44s-v5-v6缺失型”表型，该表型与疾病晚期阶段相关。
肿瘤(癌症)患者之家