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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 9/2019

01-09-2019 | Ovarian Cancer | Original Article

Lymphocyte-specific kinase expression is a prognostic indicator in ovarian cancer and correlates with a prominent B cell transcriptional signature

Authors: Emily Hinchcliff, Cherie Paquette, Jason Roszik, Sarah Kelting, Mark H. Stoler, Samuel C. Mok, Tsz-Lun Yeung, Qian Zhang, Melinda Yates, Weiyi Peng, Patrick Hwu, Amir Jazaeri

Published in: Cancer Immunology, Immunotherapy | Issue 9/2019

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Abstract

Objective

To investigate the prognostic and biologic significance of immune-related gene expression in high grade serous ovarian cancer (HGSOC).

Methods

Gene expression dependent survival analyses for a panel of immune related genes were evaluated in HGSOC utilizing The Cancer Genome Atlas (TCGA). Prognostic value of LCK was validated using IHC in an independent set of 72 HGSOC. Prognostic performance of LCK was compared to cytolytic score (CYT) using RNAseq across multiple tumor types. Differentially expressed genes in LCK high samples and gene ontology enrichment were analyzed.

Results

High pre-treatment LCK mRNA expression was found to be a strong predictor of survival in a set of 535 ovarian cancers. Patients with high LCK mRNA expression had a longer median progression free survival (PFS) of 29.4 months compared to 16.9 months in those without LCK high expression (p = 0.003), and longer median overall survival (OS) of 95.1 months versus 44.5 months (p = 0.001), which was confirmed in an independent cohort by IHC (p = 0.04). LCK expression was compared to CYT across tumor types available in the TCGA and was a significant predictor of prognosis in HGSOC where CYT was not predictive. Unexpectedly, LCK high samples also were enriched in numerous immunoglobulin-related and other B cell transcripts.

Conclusions

LCK is a better prognostic factor than CYT in ovarian cancer. In HGSOC, LCK high samples were characterized by higher expression of immunoglobulin and B-cell related genes suggesting that a cooperative interaction between tumor infiltrating T and B cells may correlate with better survival in this disease.
Appendix
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Metadata
Title
Lymphocyte-specific kinase expression is a prognostic indicator in ovarian cancer and correlates with a prominent B cell transcriptional signature
Authors
Emily Hinchcliff
Cherie Paquette
Jason Roszik
Sarah Kelting
Mark H. Stoler
Samuel C. Mok
Tsz-Lun Yeung
Qian Zhang
Melinda Yates
Weiyi Peng
Patrick Hwu
Amir Jazaeri
Publication date
01-09-2019
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 9/2019
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-019-02385-x

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