Expression of deltaNp73 and TAp73alpha independently associated with radiosensitivities and prognoses in cervical squamous cell carcinoma.
OBJECTIVE
The p73 gene produces different protein isoforms using alternative promoters and splicing, which have different biological characteristics. This study was to investigate the expression patterns of two distinct p73 isoforms (deltaNp73 and TAp73alpha) in cervical squamous cell carcinomas (SCC) and the relationship between their expressions and prognostic significance in cervical SCC patients.


METHODS
We investigated the protein expressions of deltaNp73 and TAp73alpha in 117 cervical SCC and 113 normal cervical tissues using immunohistochemistry. The expression levels were analyzed with clinical variables and patients' survival.


RESULTS
DeltaNp73and TAp73alpha were significantly overexpressed in cervical SCC compared with those in normal cervical epithelium (P < 0.001). However, their expressions were inversely correlated (P < 0.001, R = -0.368) and associated with differential tumor radiosensitivity. Overexpression of deltaNp73 was significantly found in SCC resistant to irradiation (P < 0.001), whereas increase of TAp73alpha expression was observed in the majority of SCC sensitive to irradiation (P < 0.001). Multivariate and survival analyses indicated that the expressions of deltaNp73 and TAp73alpha were independently associated with prognosis: deltaNp73 was associated with recurrence of the disease [P = 0.001; odds ratio (OR), 4.857] and an adverse outcome (P = 0.012; OR, 4.676), whereas TAp73alpha predicted a better survival of cervical SCC patients (P = 0.018; OR, 0.065).


CONCLUSIONS
The p73 gene might be an important determinant of cellular response to irradiation. The expressions of the two main isoforms (deltaNp73 and TAp73alpha) might be potential markers for predicting the prognosis and sensitivity to radiotherapy in patients with cervical SCC.
Liu
Stephanie Si
SS
Department of Obstetrics and Gynaecology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.
Chan
Kelvin Yuen-Kwong
KY
Cheung
Annie Nga-Yin
AN
Liao
Xiao-Yun
XY
Leung
Tsin-Wah
TW
Ngan
Hextan Yuen-Sheung
HY
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D002584:Cervix Uteri / Q000166:cytology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D020033:Protein Isoforms; D015996:Survival Rate; D013997:Time Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000628:therapy
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C000606369:delta Np73 protein, human