title: Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
abstract: Lymph node metastasis indicates poor prognosis in esophageal cancer. To understand the underlying mechanisms, most studies so far focused on investigating the tumors themselves and/or invaded lymph nodes. However they neglected the potential events within the metastatic niche, which precede invasion. Here we report the first description of these regulations in patients on transcription level. We determined transcriptomic profiles of still metastasis-free regional lymph nodes for two patient groups: patients classified as pN1 (n = 9, metastatic nodes exist) or pN0 (n = 5, no metastatic nodes exist). All investigated lymph nodes, also those from pN1 patients, were still metastasis-free. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients--even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
authors.affiliation: Department of Internal Medicine, Center for Internal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Department of Clinical Chemistry, Center for Diagnostic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Otto
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Center for Surgical Sciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Koenig
authors.affiliation: Department of Otolaryngology - Head and Neck Surgery, CHUV, University of Lausanne, Lausanne, Switzerland.
authors.forename: Genrich V
authors.initials: GV
authors.lastname: Tolstonog
authors.affiliation: Department of Osteology and Biomechanics, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Jeschke
authors.affiliation: Department of Clinical Chemistry, Center for Diagnostic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kristin
authors.initials: K
authors.lastname: Klaetschke
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Center for Surgical Sciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Yogesh K
authors.initials: YK
authors.lastname: Vashist
authors.affiliation: Department of Anatomy and Experimental Morphology, Center for Experimental Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Wicklein
authors.affiliation: Department of Clinical Chemistry, Center for Diagnostic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
authors.affiliation: Department of General, Visceral and Thoracic Surgery, Center for Surgical Sciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Jakob R
authors.initials: JR
authors.lastname: Izbicki
authors.affiliation: Department of Clinical Chemistry, Center for Diagnostic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Streichert
mesh_terms: D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D004947:Esophagus / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis* / Q000235:genetics*; D059467:Transcriptome
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins