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Series GSE26511 Query DataSets for GSE26511
Status Public on Feb 15, 2011
Title Involvement of the TGF-β and β-catenin pathways in pelvic lymph node metastasis in early stage cervical cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Purpose: Presence of pelvic lymph node metastases is the main prognostic factor in early stage cervical cancer patients, primarily treated with surgery. Aim of this study was to identify cellular tumor pathways associated with pelvic lymph node metastasis in early stage cervical cancer.
Experimental Design: Gene expression profiles (Affymetrix U133 plus 2.0) of 20 patients with negative (N0) and 19 with positive lymph nodes (N+), were compared with gene sets that represent all 285 presently available pathway signatures. Validation immunostaining of tumors of 274 consecutive early stage cervical cancer patients was performed for representatives of the identified pathways.
Results: Analysis of 285 pathways resulted in identification of five pathways (TGF-β, NFAT, ALK, BAD, and PAR1) that were dysregulated in the N0, and two pathways (β-catenin and Glycosphingolipid Biosynthesis Neo Lactoseries) in the N+ group. Class comparison analysis revealed that five of 149 genes that were most significantly differentially expressed between N0 and N+ tumors (P<0.001) were involved in β-catenin signaling (TCF4, CTNNAL1, CTNND1/p120, DKK3 and WNT5a). Immunohistochemical validation of two well-known cellular tumor pathways (TGF-β and β-catenin) confirmed that the TGF-β pathway (positivity of Smad4) was related to N0 (OR:0.20, 95%CI:0.06-0.66) and the β-catenin pathway (p120 positivity) to N+ (OR:1.79, 95%CI:1.05-3.05).
Conclusions: Our study provides new, validated insights in the molecular mechanism of lymph node metastasis in cervical cancer. Pathway analysis of the microarray expression profile suggested that the TGF-β and p120-associated non-canonical β-catenin pathways are important in pelvic lymph node metastasis in early stage cervical cancer.
Overall design For the microarray experiment, we selected fresh frozen primary cervical cancer tissue, containing at least 80% tumor cells, of patients with histologically confirmed N0 (n=20) and of patients with N+ (n=19). The N0 and N+ groups were matched for age, FIGO stage and histology (all squamous cell carcinoma).
Contributor(s) Noordhuis MG, Fehrmann RS, Wisman GB, Nijhuis ER, van Zanden JJ, Moerland PD, Ver Loren van Themaat E, Volders HH, Kok M, ten Hoor KA, Hollema H, de Vries EG, de Bock GH, van der Zee AG, Schuuring E
Citation(s) 21385933
Submission date Jan 10, 2011
Last update date Mar 25, 2019
Contact name Maartje Noordhuis
Organization name University Medical Center Groningen
Department Gynecologic Oncology
Street address PObox 30.001
City Groningen
ZIP/Postal code 9700RB
Country Netherlands
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (39)
GSM651831 Cervical cancer-lymph node negative-01-01
GSM651832 Cervical cancer-lymph node negative-02-02
GSM651833 Cervical cancer-lymph node negative-03-11
BioProject PRJNA136693

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Supplementary file Size Download File type/resource
GSE26511_RAW.tar 335.7 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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