Galectin-1 is associated with poor prognosis in patients with cutaneous head and neck cancer with perineural spread

Chawla, Sharad, Warren, Timothy A., Wockner, Leesa F., Lambie, Duncan L. J., Brown, Ian S., Martin, Thomas P. C., Khanna, Rajiv, Leggatt, Graham R. and Panizza, Benedict J. (2016) Galectin-1 is associated with poor prognosis in patients with cutaneous head and neck cancer with perineural spread. Cancer Immunology, Immunotherapy, 65 2: 213-222. doi:10.1007/s00262-015-1788-z

Author Chawla, Sharad
Warren, Timothy A.
Wockner, Leesa F.
Lambie, Duncan L. J.
Brown, Ian S.
Martin, Thomas P. C.
Khanna, Rajiv
Leggatt, Graham R.
Panizza, Benedict J.
Title Galectin-1 is associated with poor prognosis in patients with cutaneous head and neck cancer with perineural spread
Journal name Cancer Immunology, Immunotherapy   Check publisher's open access policy
ISSN 1432-0851
Publication date 2016-02-01
Year available 2017
Sub-type Article (original research)
DOI 10.1007/s00262-015-1788-z
Open Access Status Not Open Access
Volume 65
Issue 2
Start page 213
End page 222
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 2723 Immunology and Allergy
2403 Immunology
2730 Oncology
1306 Cancer Research
Abstract Lipids are known to influence tumour growth, inflammation and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients. Unsupervised analysis of lipidomic profiles (323 lipid species) classified the Phase 1 cohort into two patient subgroups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, p = 0.0005). The levels of 46 lipids were individually prognostic and were predominantly sphingolipids with higher levels associated with poor prognosis. A prognostic three-lipid signature was derived (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0) and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, p = 0.0003). The signature was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics. The association of plasma lipids with CRPC prognosis suggests a possible role of these lipids in disease progression. Further research is required to determine if therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome.
Formatted abstract
Spread of head and neck cancer along the cranial nerves is often a lethal complication of this tumour. Current treatment options include surgical resection and/or radiotherapy, but recurrence is a frequent event suggesting that our understanding of this tumour and its microenvironment is incomplete. In this study, we have analysed the nature of the perineural tumour microenvironment by immunohistochemistry with particular focus on immune cells and molecules, which might impair anti-tumour immunity. Moderate to marked lymphocyte infiltrates were present in 58.8 % of the patient cohort including T cells, B cells and FoxP3-expressing T cells. While human leukocyte antigen (HLA) class I and more variably HLA class II were expressed on the tumour cells, this did not associate with patient survival or recurrence. In contrast, galectin-1 staining within lymphocyte areas of the tumour was significantly associated with a poorer patient outcome. Given the known role of galectin-1 in immune suppression, the data suggest that galectin inhibitors might improve the prognosis of patients with perineural spread of cancer.
Keyword Oncology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1042095
PG 10-01
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Medicine Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 6 times in Scopus Article | Citations
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Created: Sat, 16 Jan 2016, 19:56:28 EST by Dr Graham Leggatt on behalf of UQ Diamantina Institute