Expression levels of hnRNP G and hTra2-beta1 correlate with opposite outcomes in endometrial cancer biology.
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.
Ouyang
Yi Qin
YQ
Department of Obstetrics and Gynecology, Freiburg University Medical Center, 79106 Freiburg, Germany.
zur Hausen
Axel
A
Orlowska-Volk
Marzenna
M
Jäger
Markus
M
Bettendorf
Herta
H
Hirschfeld
Marc
M
Tong
Xiao Wen
XW
Stickeler
Elmar
E
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
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