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A Preliminary Study Of Candiadate Tumor Markers PRDX1, PPIA, MnSOD And FABP5 For Mycosis Fungoides

Posted on:2012-02-06Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y P CengFull Text:PDF
GTID:1114330335982153Subject:Dermatology and Venereology
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BackgroundsMycosis fungoides is the most common type of primary cutaneous lymphomas. MF is characterized by epidermotropism of small to medium-sized lymphocytic cells which have a "cerebriform" nucleus. Due to similarities with benign lymphoproliferative or reactive skin diseases, especially at the initial presentation of the disease, diagnosis can be difficult. Up to now, there is no highly specific tumour marker for MF and only a limited number of biologic markers for therapeutic effectiveness observation and prognosis evaluation. Proteomic techniques have been used in the study of tumor markers for MF in the last few years. In our previous study, we used 2-DE combined with matrix assisted laser desorption ionization/time of flight-mass spectrometry (MALDI-TOF-MS) to compare global protein expression patterns in lesional skin from patients with MF and normal skin from healthy individuals. Thirty-one differential expressed proteins were identified. Of these proteins, three upregulated proteins in MF were identified in multiple groups including manganese superoxide dismutase (MnSOD), fatty acid-binding protein 5 (FABP5) and S100A8. Thereafter, the total protein lysates were obtained from MF lesional skin tissues and normal skin tissues. Overexpressions of theses proteins in MF lesional skin tissues were then verified by Western blot (WB).Objectives(1) To further verify the differential expressions of peroxiredoxin 1 (PRDX1) and peptidylprolyl isomerase A (PPIA) identified by our previous MALDI mass spectrum study between MF lesional skin tissues and normal skin tissues.(2) To localize the sites of differential expressions of PRDX1, PPIA, MnSOD and FABP5 between MF lesional skin tissues and normal skin tissues.(3) To find differential expressed proteins in the lymphocytes of MF and investigate their expressions in cutaneous T cell lymphoma (CTCL) cell line Hut-78 cultured in vitro.Methods(1) The total protein lysates were obtained from MF lesional skin tissues and normal skin tissues and were analysed by WB to dectect the expressions of PRDX1 and PPIA.(2) Immunohistochemistry (IHC) was used to localize the sites of differential expressions of PRDX1, PPIA, MnSOD and FABP5 between MF lesional skin tissues and normal skin tissues.(3) The differential expressed proteins found in the lymphocytes of MF were detected by WB and IHC in PBMCs from healthy volunteers and Hut-78 cells.Results(1) PRDX1 protein was overexpressed in dermal lymphocytes of MF lesional tissues; the expression of PPIA showed no difference between MF group and normal control group; MnSOD protein was overexpressed in the epidermis and dermal lymphocytes of MF lesional tissues; FABP5 protein was highly expressed in the epidermis of MF lesional tissues.(2) Compared with PBMCs from healthy volunteers, PRDX1 protein was upregulated in Hut-78 cells, while MnSOD protein was downregulated.Conclusions(1) PRDX1 and MnSOD might be potential tumor markers for MF.(2) PPIA and FABP5 are not reliable tumor markers for MF.(3) The expression of MnSOD in cutaneous malignant T cell might be influenced by the culture microenvironment in vitro.
Keywords/Search Tags:mycosis fungoides, tumor marker, PRDXl, PPIA, MnSOD, FABP5, Hut-78
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