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12.09.2019 | Original Article

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

Zeitschrift:
Cancer Immunology, Immunotherapy
Autoren:
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
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s00262-019-02385-x) contains supplementary material, which is available to authorized users.
Some of the results included in this paper were previously presented in poster format at the Society of Gynecologic Oncology (SGO) National Meeting (Honolulu Hawaii USA, March 2019) and as an oral presentation at the Gynecologic Oncology National Fellow’s Forum (Miami Florida USA, May 2019) [1].

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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.

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Supplementary material 1 (PDF 7205 kb)
262_2019_2385_MOESM1_ESM.pdf
Literatur
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