Expression of lipid signalling molecules in epithelial and lymphoid malignancies

Abdullah, Maizaton Atmadini (2014). Expression of lipid signalling molecules in epithelial and lymphoid malignancies. University of Birmingham. Ph.D.

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Abstract

Proteins which regulate the expression and activity of the small oncogenic lipids, LPA and S1P are important in the development and progression of cancers. This study set out to explore the expression of lipid signalling molecules in two types of lymphoid malignancies and a few epithelial malignancies and correlate their association with clinicopathological parameters. The expression of SPHK1, S1PR1, ABCC1 and ATX in epithelial malignancies were studied which included breast, bladder and lung cancer. It is shown that S1PR1 is a poor prognostic marker in breast cancer and ATX is a poor prognostic marker in both breast and lung cancers. The expression of lipid signalling proteins and mRNA showed that S1PR1 was commonly expressed in HL, while S1PR3 was expressed in all HL cases suggesting its role in lymphomagenesis. L591 Hodgkin lymphoma cells treated with anti-S1P, Sphingomab showed restoration of four B cell receptor genes namely BCL10, RAPGEF1, NFATC3 and MALT by gene expression microarray. Sphingomab also showed downregulation of S1PR3 and S1PR5 genes which may be a possible therapeutic target in cancer. The incidence of EBV+ DLBCL in this series is 14/300 (4.7%). S1PR1 was commonly expressed in DLBCL and patients with S1PR1 expressing tumours were more likely to have more than one extranodal site involvement. EBV positivity, presence of B symptoms, bulky disease, BCL6 positivity and high IPI were found to be poor prognostic factors in DLBCL.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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