Polymerase eta mRNA expression predicts survival of non-small cell lung cancer patients treated with platinum-based chemotherapy.
OBJECTIVE
The effect of translesion DNA synthesis system in conferring cellular tolerance to DNA-damaging agents has been recently described. DNA polymerase eta (Pol eta) is part of this machinery and in vitro models showed that it can overcome DNA damages caused by cisplatin and UV rays. The aim of the present study was to investigate the role of Pol eta mRNA expression levels in non-small cell lung cancer (NSCLC).


METHODS
Pol eta mRNA expression levels were evaluated by real-time PCR in (a) formalin-fixed paraffin-embedded biopsies of 72 NSCLC patients treated with platinum-based chemotherapy, (b) fresh snap-frozen surgical specimens of tumor and corresponding normal lung tissue from 50 consecutive patients not treated with perioperative or postoperative chemotherapy, and (c) five NSCLC cell lines.


RESULTS
High Pol eta expression levels were strongly associated with shorter survival at both univariate (6.9 versus 21.1 months; P = 0.003) and multivariate (hazard ratio, 3.18; 95% confidence interval, 1.73-5.84; P = 0.008) analysis in the group of platinum-treated patients. By contrast, Pol eta expression was not significantly correlated with the prognosis in surgically resected patients (P = 0.54) and mRNA levels did not significantly differ in tumor versus normal lung (P = 0.82). Moreover, endogenous Pol eta mRNA expression was found to be inducible by cisplatin in three of five cell lines and significantly associated with in vitro sensitivity (P = 0.01).


CONCLUSIONS
Taken together, these data indicate Pol eta as a predictive rather than prognostic marker worth of further investigation in NSCLC patients candidate to platinum-based chemotherapy.
Ceppi
Paolo
P
Thoracic Oncology Unit, Department of Clinical and Biological Sciences, University of Turin, San Luigi Hospital, Orbassano (Torino), Italy. paolo.ceppi@unito.it
Novello
Silvia
S
Cambieri
Alberto
A
Longo
Marina
M
Monica
Valentina
V
Lo Iacono
Marco
M
Giaj-Levra
Matteo
M
Saviozzi
Silvia
S
Volante
Marco
M
Papotti
Mauro
M
Scagliotti
Giorgio
G
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D016896:Treatment Outcome; D000099270:Y-Family DNA Polymerases
D002945:Cisplatin; D004259:DNA-Directed DNA Polymerase; D012333:RNA, Messenger; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases