[Expression and predictive role of excision repair cross complementation group 1, ribonucleotide reductase subunit M1, and β-tubulin 3 in postoperative patients with non-small cell lung cancer receiving adjuvant chemotherapy].
OBJECTIVE
To determine the predictive value of excision repair cross complementation group 1 (ERCC1),ribonucleotide reductase subunit M1 (RRM1), and β-tubulin 3 expressions in postoperative patients with stage 1- 3 non-small cell lung cancer (NSCLC) receiving adjuvant chemotherapy.


METHODS
All NSCLC patients received surgery therapy followed by at least one cycle of adjuvant chemotherapy in our hospital from January 2004 to December 2007. The expressions of ERCC1, RRM1, and β-tubulin 3 were detected by immunohistochemical methods. The relationships among clinicopathologic characteristics, chemotherapy regimens,biomarkers' expressions and disease-free survival (DFS) were analyzed.


RESULTS
The high-expression rates of ERCC1, RRM1, and β-tubulin 3 were 36.4%,43.7%,and 38.4%,respectively. The expressions of these three biomarkers were not correlated. After a median follow-up of 35.8 months, 80 patients experienced metastatic or recurrent tumors and 40 patients died. The median overall survival was not reached and the median DFS was 24.1 months. Univariate survival analysis showed that sex, clinical stage,and adenocarcinoma or not were related to DFS, while age, smoke history, chemotherapy regimens, and expression levels of ERCC1, RRM1, and β-tubulin 3 has no prognostic significance in these surgically resected NSCLC patients who were receiving adjuvant chemotherapy. Male (P=0.036), earlier clinical stage (P=0.001), and non-adenocarcinoma (P=0.004) predicted better DFS. Stratified analysis indicated that in RRM1 high-expression strata,the regimens with gemcitabine had curtailed DFS compared with other regimens (P=0.054); in β-tubulin 3 high-expression strata,the regimens containing taxane (including paclitaxel and docetaxel subgroups) had curtailed DFS compared with other regimens (P=0.076), although there was no statistical significance. However,there were no similar predictive significance in RRM1 and β-tubulin 3 low-expression strata or in ERCC1 strata with different expression levels. COX proportional regression analysis showed that adenocarcinoma or not and clinical stage were independent risk factors of DFS in this population.


CONCLUSIONS
In postoperative NSCLC patients who are receiving adjuvant chemotherapy, patients with high expression of RRM1 tends to be resistant to gemcitabine and patients with high expression of β-tubulin 3 tends to be resistant to taxane drugs. ERCC1, RRM1, and β-tubulin 3 detected by immunohistochemistry can be biomarkers to help to choose better chemotherapy regimen and predict the effectiveness of adjuvant chemotherapy.
Shi
Yan
Y
Department of Medical Oncology, PLA General Hospital, Beijing 100853, China.
Chen
Li
L
Li
Jie
J
Lü
Ya-li
YL
Jiao
Shun-chang
SC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012262:Ribonucleoside Diphosphate Reductase; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D014404:Tubulin; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C071447:ERCC1 protein, human; D004720:Endonucleases