Schrevel Marlies, Corver Willem E, Vegter Margit E, Ter Haar Natalja T, Dreef Enno J, Beltman Jogchum J, Kenter Gemma, Bosse Tjalling, de Kroon Cornelis D, Jordanova Ekaterina S
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
Oncotarget. 2017 Sep 18;8(50):87568-87581. doi: 10.18632/oncotarget.20976. eCollection 2017 Oct 20.
L1 cell adhesion molecule (L1CAM) has been shown to be a prognostic marker in various cancer types, and has been suggested to play a role in epithelial mesenchymal transition (EMT). Here, we determined the prognostic significance of L1CAM in cervical cancer and its association with vimentin expression on tumor cells, indicative of EMT.
Formalin-fixed, paraffin-embedded primary tumor samples from 372 cervical cancer patients were collected for immunohistochemical analysis of L1CAM expression. In 109 FFPE specimens, the percentage of vimentin expressing tumor cells was determined by flow cytometry.
Positive L1CAM expression (≥10% of tumor cells) was associated with disease-free survival, validated using RNAseq TCGA data. L1CAM expression was independently associated with locoregional recurrence-free survival (hazard ratio 2.62, 95% CI 1.33 - 5.17, = 0.006), and strongly associated with percentage of vimentin expressing tumor cells ( = 0.003). Expression of both L1CAM and vimentin indicated a subgroup with the highest risk of recurrence (hazard ratio 3.15, 95% CI 1.25 - 7.92, = 0.015).
L1CAM might be a promising new prognostic marker for locoregional recurrences in cervical cancer, and its association with vimentin expression suggests that L1CAM might affect tumor aggressiveness, possibly through EMT.
L1细胞粘附分子(L1CAM)已被证明是多种癌症类型的预后标志物,并被认为在上皮-间质转化(EMT)中发挥作用。在此,我们确定了L1CAM在宫颈癌中的预后意义及其与肿瘤细胞波形蛋白表达的相关性,波形蛋白表达可指示EMT。
收集372例宫颈癌患者的福尔马林固定、石蜡包埋的原发性肿瘤样本,用于L1CAM表达的免疫组织化学分析。在109个福尔马林固定石蜡包埋标本中,通过流式细胞术确定波形蛋白表达肿瘤细胞的百分比。
L1CAM阳性表达(≥10%的肿瘤细胞)与无病生存期相关,这一结果通过RNAseq TCGA数据得到验证。L1CAM表达与局部区域无复发生存期独立相关(风险比2.62,95%可信区间1.33 - 5.17,P = 0.006),并与波形蛋白表达肿瘤细胞的百分比密切相关(P = 0.003)。L1CAM和波形蛋白的表达均表明存在一个复发风险最高的亚组(风险比3.15,95%可信区间1.25 - 7.92,P = 0.015)。
L1CAM可能是宫颈癌局部区域复发的一个有前景的新预后标志物,其与波形蛋白表达的相关性表明L1CAM可能通过EMT影响肿瘤侵袭性。