title: IL-6 and IL-11 as markers for tumor aggressiveness and prognosis in gastric adenocarcinoma patients without mutations in Gp130 subunits.
abstract: OBJECTIVE
  A point mutation (gp130Y757F/Y759F) was identified as being responsible for aberrant activation of gp130 in mice and associated with gastric adenocarcinoma induction. As a result, we investigated the possible role of key point mutations in Tyr from IL6ST exon 17 that encode for the catalytic domain of gp130, and of its respective activators (IL-6 family member cytokines) in human gastric cancer initiation and development.
  
  
  METHODS
  DNA, protein and plasma from 51 patients with gastric adenocarcinoma have been used in exploring gp130 status. We used sequencing analysis of IL6ST exon 17 in order to identify possible mutations that would lead to constitutive active forms of the receptor. The levels of gp130 activators (IL-6, IL-11, LIF) were analyzed by ELISA in plasma and mucosa of patients with gastric adenocarcinoma.
  
  
  RESULTS
  Sequencing analysis did not identify mutations in gp130 key positions (Y759, Y767, Y814, Y905 and Y915). An increased IL-6 and IL-11 level in gastric mucosa was observed, correlated with staging, indicating these cytokines as gp130 activators in tumor epithelial cell. Those variations were consistent with increased IL-6 level in plasma. Furthermore, IL-6, but not IL-11 showed a significant correlation with patient's survival time, suggesting that tissue and plasma concentration of IL-6 might be a marker of tumor aggressiveness with prognostic value.
  
  
  CONCLUSIONS
  According to our results, no mutations were detected in gp130 key positions in human gastric adenocarcinoma samples. However, gp130 activation may occur due to the increased level of IL-6 and IL-11 cytokines detected that can become valuable biomarkers.
authors.affiliation: Stefan S. Nicolau Institute of Virology, Bucharest, Romania.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Necula
authors.forename: Mihaela
authors.initials: M
authors.lastname: Chivu-Economescu
authors.forename: Elena L
authors.initials: EL
authors.lastname: Stanciulescu
authors.forename: Coralia
authors.initials: C
authors.lastname: Bleotu
authors.forename: Simona O
authors.initials: SO
authors.lastname: Dima
authors.forename: Irina
authors.initials: I
authors.lastname: Alexiu
authors.forename: Adriana
authors.initials: A
authors.lastname: Dumitru
authors.forename: Gabriel
authors.initials: G
authors.lastname: Constantinescu
authors.forename: Irinel
authors.initials: I
authors.lastname: Popescu
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Diaconu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016022:Case-Control Studies; D050822:Cytokine Receptor gp130 / Q000235:genetics*; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005819:Genetic Markers; D016481:Helicobacter Infections / Q000150:complications / Q000175:diagnosis; D016480:Helicobacter pylori / Q000302:isolation & purification; D006801:Humans; D017370:Interleukin-11 / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011379:Prognosis; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality
chemical_list: D014408:Biomarkers, Tumor; D005819:Genetic Markers; C494199:IL6ST protein, human; D017370:Interleukin-11; D015850:Interleukin-6; D050822:Cytokine Receptor gp130