Bio-P-02 - Genetic expression profile in the prognosis of mycosis fungoides

Abstract

We present a historic cohort study with 57 patients diagnosed with mycosis fungoides in early stages during the years 1999 to 2002. Our group performed a cDNA microarray on the diagnosis skin biopsies samples with the CNIO (oncologic investigation national center of Spain) Onco-Chip. This chip includes 6386 cancer-related clones. Since the samples were processed in two deferent years the initial set of 57 patients was divided in two groups of 29 and 28 patients due to the heterogeneity of the sample array results. The patients had a medium of 14 years of follow-up and were divided in two groups: progression (development of tumor, nodes, erythroderma, blood involvement or metastasis) and no progression. And we performed volcano pot analysis and GSEA to determine whether there are different genes expressions at diagnosis that determine prognosis. Several pathways were up and down regulated differently in patients progressing. We performed a GSEA analysis with the following results. Pathways related with progression: CXCR4 pathway (p=0.000) Normalized Enrichment Score (NES) 1.91 and FDR 0.027; genes: BCAR1, PXN, PIK3CA, PTK2, PIK3R1, PRKCA, HRAS, RAF1, CXCL12, PIK3C2G, GNB1. Other pathways with p<5% were: ERK5 pathway p=0.035, NES 1.15, FDR 0.92; genes: PIK3CA, PIK3R1, HRAS, RPS6KA1, SHC1. AKT pathway p=0.049, NES 1.52, FDR 0.70; genes: PIK3CA, PIK3R1, GHR, CASP9, YWHAH. Cytokine pathway p=0.034, NES 1.49, FDR 0.66; genes: SOCS6, SOD2, CCL2. PIK 3-CL1 pathway p=0.035, NES 1.39, FDR 0.63; genes: PIK3CA and PIK3CD INFAR1 pathway p=0.012, NES –1.51, FDR 1; genes: IFNAR1, JAK1, IFNAR2. P53 pathway p=0.032, NES –1.48, FDR 1; genes: MDM2, ABCB1, TP53. Pathways related with no progression: lymphocyte pathway p=0.000, FDR 0.31 NES –1.67; genes: ITGA, ITGB1, SELL, SELP. UV response pathway p=0.007, NES 1.62, FDR 0.40; genes: NTRK3, CCNE1, RAB27A, LYN, CEBPG, IL6ST, GAL, PSMC3, RRAD, ATF3, SOD2, BAK1, STIP1, GCH1, BMP2, PRKCD, RFC4, E2F2, IRF1, RASGRP1, BTG3, CDKN1C, ATP6V1F, CHKA, EIF5, POLE3, CDC5, UROD, CDC34, NR4A1, ENO2, JUNB, SLC6A8, DNAJB1, IGFB2, CDK2, PPIF, ABCB1, RXRB, PPT1, SPOP, KIT, MET, EIF5, FURIN. Other pathway with p<5% was: ERK pathway p=0.048, NES –1.48, FDR 0.93; genes: SRC, NGFB, HRAS; IGF1R, RPS6KA1, MYC, EGFR, RAF, SHC1, PDGFRA, GNB1, STAT3, NGFR, ITGB1, GNAS. We also performed a volcano pot study that showed overexpression of PPP1R3C a gene related with the mTOR pathway in the progression cases. Although our sample size was limited, we believe that pathways related with JAK/STAT, PIK/AKT/mTOR, MAPK, and cellular cycle can be differentially expressed in patients that have progression of the disease from the early stages of mycosis fungoides. Further studies are necessary to validate our results.