title: Expression levels of hnRNP G and hTra2-beta1 correlate with opposite outcomes in endometrial cancer biology.
abstract: HnRNP G is a member of heterogeneous nuclear ribonucleoprotein (hnRNP) family with potent tumor suppressive activities. Human transformer-2-beta1 (hTra2-beta1) belongs to the arginine-serine rich like proteins and is found over-expressed in various human cancers. It was recently shown that hnRNP G and hTra2-beta1 exert antagonistic effects on alternative splicing. In our study we explored the impact of these two factors in tumor biology of endometrial cancer (EC). EC tissues (n = 139) were tested for hnRNP G and hTra2-beta1 expression on mRNA level by real time PCR and on protein level by immunohistochemistry. HTra2-beta1 mRNA level was found being induced in advanced International Federation of Gynecology and Obstetrics (FIGO) stages (p = 0.016). HnRNP G protein nuclear expression was found more prominent in patients without distant organ metastases (p = 0.033) and in FIGO Stages I/II group (p < 0.001). HTra2-beta1 protein nuclear levels were elevated in poorly differentiated (p = 0.044) and lymph node metastases (p = 0.003) cancers. Kaplan-Meier survival curves revealed that elevated hnRNP G mRNA (p = 0.029) and protein (p = 0.022) levels were associated with a favorable patient outcome. Multivariate Cox-regression analyses identified nuclear hnRNP G level [hazard ratio (HR) 0.468, p = 0.026) as well as hTra2-beta1 level (hazard ratio 5.760, p = 0.004) as independent prognostic factors for EC progression-free survival. Our results indicate that the antagonistic functional effects of hnRNP G and hTra2-beta1 on alternative splicing correlate directly to their opposite clinical effects on EC patient outcome.
authors.affiliation: Department of Obstetrics and Gynecology, Freiburg University Medical Center, 79106 Freiburg, Germany.
authors.forename: Yi Qin
authors.initials: YQ
authors.lastname: Ouyang
authors.forename: Axel
authors.initials: A
authors.lastname: zur Hausen
authors.forename: Marzenna
authors.initials: M
authors.lastname: Orlowska-Volk
authors.forename: Markus
authors.initials: M
authors.lastname: Jäger
authors.forename: Herta
authors.initials: H
authors.lastname: Bettendorf
authors.forename: Marc
authors.initials: M
authors.lastname: Hirschfeld
authors.forename: Xiao Wen
authors.initials: XW
authors.lastname: Tong
authors.forename: Elmar
authors.initials: E
authors.lastname: Stickeler
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D005260:Female; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068103:Serine-Arginine Splicing Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009419:Nerve Tissue Proteins; C510272:RBMX protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C097083:TRA2B protein, human; D000068103:Serine-Arginine Splicing Factors