1. Low junctional adhesion molecule-A expression is associated with an epithelial to mesenchymal transition and poorer outcomes in high-grade serous carcinoma of uterine adnexa
- Author
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Communal, Laudine, Medrano, Mauricio, Sircoulomb, Fabrice, Paterson, Joshua, Köbel, Martin, Rahimi, Kurosh, Hoskins, Paul, Tu, Dongsheng, Lheureux, Stephanie, Oza, Amit, Ailles, Laurie, Provencher, Diane, Rottapel, Robert, and Mes-Masson, Anne-Marie
- Abstract
High-grade serous carcinoma of uterine adnexa (HGSC) is the most frequent histotype of epithelial ovarian cancer and has a poor 5-year survival rate due to late-stage diagnosis and the poor efficacy of standard treatments. Novel biomarkers of cancer outcome are needed to identify new targetable pathways and improve personalized treatments. Cell-surface screening of 26 HGSC cell lines by high-throughput flow cytometry identified junctional adhesion molecule 1 (JAM-A, also known as F11R) as a potential biomarker. Using a multi-labeled immunofluorescent staining coupled with digital image analysis, protein levels of JAM-A were quantified in tissue microarrays from three HGSC patient cohorts: a discovery cohort (n= 101), the Canadian Ovarian Experimental Unified Resource cohort (COEUR, n= 1158), and the Canadian Cancer Trials Group OV16 cohort (n= 267). Low JAM-A level was associated with poorer outcome in the three cohorts by Kaplan–Meier (p= 0.023, p< 0.001, and p= 0.036, respectively) and was an independent marker of shorter survival in the COEUR cohort (HR = 0.517 (0.381–703), p< 0.001). When analyses were restricted to patients treated by taxane–platinum-based chemotherapy, low JAM-A protein expression was associated with poorer responses in the COEUR (p< 0.001) and OV16 cohorts (p= 0.006) by Kaplan–Meier. Decreased JAM-Agene expression was an indicator of poor outcome in gene expression datasets including The Cancer Genome Atlas (n= 606, p= 0.002) and Kaplan–Meier plotter (n= 1816, p= 0.024). Finally, we observed that tumors with decreased JAM-A expression exhibited an enhanced epithelial to mesenchymal transition (EMT) signature. Our results demonstrate that JAM-A expression is a robust prognostic biomarker of HGSC and may be used to discriminate tumors responsive to therapies targeting EMT.
- Published
- 2020
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