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MicroRNA expression profile related to lymph node status in women with stage grade 1-2-3 endometrial cancer

ABSTRACT: The aim of this study was to evaluate whether microRNA profiles of grade 1 – 2 or 3 endometrioid adenocarcinomas can be related to nodal status and used as a tool to adapt surgical staging in early-stage EC. MicroRNA expression were assessed in twelve formalin-fixed paraffin-embedded (FFPE) EC primary tumors with positive lymph node and in 36 FFPE EC primary tumors with negative lymph node, matched for grade, stage and lymphovascular space involvement status.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE75968 | GEO | 2016/06/01

SECONDARY ACCESSION(S): PRJNA305874

REPOSITORIES: GEO

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Project description:Current prognostic factors are insufficient for precise risk-discrimination in breast cancer patients with low grade breast tumors, which, in disagreement with theoretical prognosis, occasionally form early lymph node metastasis. To identify markers for this group of patients, we employed iTRAQ-2DLC-MS/MS proteomics to 24 lymph node positive and 24 lymph node negative grade 1 luminal A primary breast tumors. Another group of 48 high-grade tumors (luminal B, triple negative, Her-2 subtypes) was also analyzed to investigate marker specificity for grade 1 luminal A tumors. From the total of 4405 proteins identified (FDR<5%), the top 65 differentially expressed together with 30 previously identified and control markers were analyzed also at transcript level. Increased levels of carboxypeptidase B1 (CPB1), PDZ and LIM domain protein 2 (PDLIM2) and ring finger protein 25 (RNF25) were associated specifically with lymph node positive grade 1 tumors, whereas stathmin 1 (STMN1) and thymosin beta 10 (TMSB10) associated with aggressive tumor phenotype also in high grade tumors at both protein and transcript level. For CPB1, these differences were also observed by immunohistochemical analysis on tissue microarrays. Upregulation of putative biomarkers in lymph node positive (vs. negative) luminal A tumors was validated by gene expression analysis of an independent published dataset (N=343) for CPB1 (p=0.00155), PDLIM2 (p=0.02027) and RELA (p=0.00015). Moreover, statistically significant connections with patient survival were identified in another public dataset (N=1678). Our findings indicate unique pro-metastatic mechanisms in grade 1 tumors that can include up-regulation of CPB1, activation of NF-κB pathway and changes in cell survival and cytoskeleton. These putative biomarkers have potential to identify the specific minor sub-population of breast cancer patients with low grade tumors who are at higher than expected risk of recurrence and who would benefit from more intensive follow-up and may require more personalized therapy.

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MicroRNA expression profile related to lymph node status in women with stage grade 1-2-3 endometrial cancer

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