Whole-transcriptome analysis of flow-sorted cervical cancer samples reveals that B cell expressed TCL1A is correlated with improved survival
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Simone Punt1, Willem E. Corver1, Sander A.J. van der Zeeuw2, Szymon M. Kielbasa3, Elisabeth M. Osse1, Henk P.J. Buermans4, Cornelis D. de Kroon5, Ekaterina S. Jordanova1,6,* and Arko Gorter1,*
1 Department of Pathology, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands
2 Department of Sequencing Analysis Support Core, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands
3 Department of Bioinformatics Center of Expertise, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands
4 Department of Leiden Genome Technology Center, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands
5 Department of Gynaecology, Leiden University Medical Center, Albinusdreef, Leiden, The Netherlands
6 Center for Gynecological Oncology Amsterdam, VUMC, De Boelelaan, Amsterdam, The Netherlands
* These authors have contributed equally to this work
Arko Gorter, email:
Keywords: uterine cervical cancer, tumor microenvironment, immune response, B lymphocytes, TCL1A
Received: May06, 2015 Accepted: June 05, 2015 Published: June 19, 2015
Cervical cancer is typically well infiltrated by immune cells. Because of the intricate relationship between cancer cells and immune cells, we aimed to identify both cancer cell and immune cell expressed biomarkers. Using a novel approach, we isolated RNA from flow-sorted viable EpCAM+ tumor epithelial cells and CD45+ tumor-infiltrating immune cells obtained from squamous cell cervical cancer samples (n = 24). Total RNA was sequenced and differential gene expression analysis of the CD45+ immune cell fractions identified TCL1A as a novel marker for predicting improved survival (p = 0.007). This finding was validated using qRT-PCR (p = 0.005) and partially validated using immunohistochemistry (p = 0.083). Importantly, TCL1A was found to be expressed in a subpopulation of B cells (CD3-/CD19+/CD10+/CD34-) using multicolor immunofluorescence. A high TCL1A/CD20 (B cell) ratio, determined in total tumor samples from a separate patient cohort using qRT-PCR (n = 52), was also correlated with improved survival (p = 0.027). This is the first study demonstrating the prognostic value of separating tumor epithelial cells from tumor-infiltrating immune cells and determining their RNA expression profile for identifying putative cancer biomarkers. Our results suggest that intratumoral TCL1A+ B cells are important for controlling cervical cancer development.
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