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Molecular Biomarkers Screened by Next-generation RNA Sequencing for non-sentinel lymph node status predicting in breast cancer patients with metastatic sentinel lymph node

ABSTRACT: Six candidates (all ER/PR+, HER2−, Ki-67 <20 %) with metastatic SLNs selected from 305 patients were equally categorized as NSLN negative and positive. We identified 103 specifically expressed genes in the NSLN negative group and 47 in the NSLN positive group. Among them, FABP1 (negative group) and CYP2A13 (positive group) were the only 2 protein-encoding genes with expression levels in the 8th to 10th deciles. Using a false discovery rate threshold of <0.05, 62 up-regulated genes and 98 down-regulated genes were discovered in the NSLN positive group. Furthermore, 10 gene fusions were identified in this group with the most frequently fused 23 gene being IGLL5.

ORGANISM(S): Homo sapiens

PROVIDER: GSE64850 | GEO | 2017/02/09

SECONDARY ACCESSION(S): PRJNA272156

REPOSITORIES: GEO

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Project description:Sentinel lymph node, the first node draining the primary tumor, is a key component of tumor microenvironment promoting immune tolerance. In melanoma, sentinel node is one of the most important prognostic factors and the most frequent site of regional metastasis. To unravel the immunomodulatory pathways that are triggered by melanoma cells in the draining node that allow tumor spreading, transcriptional profiles associated to disease progression were analyzed in archival sentinel node biopsies (SNB). Gene expression profiles of melanoma-positive and negative SNB selected to maximize the differences in terms of disease stage and course, revealed subgroups correlating with regional node involvement and disease progression within positive biopsies. Transcriptional profiles revealed that genes showing differential expression between tumor-positive SNB with/without disease progression were mainly related to inflammatory response and that were mostly down regulated in patients with poor prognosis. TNFRSF8 encoding CD30 showing up regulation in SNB from patients with progressing disease displayed higher expression by immunohistochemical staining compared to SNB from non progressing patients. Subpopulations of CD30 positive CD4/CD8 double negative and CD4 Foxp3/PD-1 CD147 positive T cells were identified by flow cytometry analysis in metastatic nodes, suggesting a potential role of regulatory and tolerogenic T cells in melanoma progression. Cutaneous melanoma patients undergoing SNB biopsy in 2001-2004 with available 5M-bM-^@M-^Syear follow-up clinical data were selected. Data relative to 752 cases was extracted, 80% (n= 603) with a negative SNB and 20% (n=149) with SNB positivity for melanoma metastases. The latter underwent regional lymphadenectomy by CLND and 30% (n=44) resulted positive for melanoma metastases at non-sentinel regional lymph nodes while 70% (n=105) resulted negative. Analysis of follow-up data showed that disease recurrence at 5 yrs occurred in 9% SNB negative patients, 14% of the patients with positive SNB resulting negative at CLND, and in 57% of the patients with positive SNB resulting positive at CLND, consistent to the range of previously reported rates (Santinami M 2009, Balch CM 2009). In order to exploit gene expression profiles to unravel molecular modifications occurring in SNB from patients with progressing disease we selected two groups of cases representing the extremes of the survey, i.e. patients positive at CLND (stage IIIB-C) recurring within 5 years follow-up (SNB-PP), and patients negative at CLND (stage IIIA-B) and non-relapsing at 5 years (SNB-PN). In addition, a group of negative SNB patients without disease recurrence at 5 years was selected and analysed for comparison as tumor negative SNB (SNB-N).

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Molecular Biomarkers Screened by Next-generation RNA Sequencing for non-sentinel lymph node status predicting in breast cancer patients with metastatic sentinel lymph node

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