RESUMEN
Although adjuvant platinum-based chemotherapy has been demonstrated to improve survival in patients with completely resected non-small cell lung cancer (NSCLC), individualized approaches to therapy are urgently required to improve the treatment efficacy and reduce unnecessary toxicity. It was hypothesized in the present study that the protein levels of excision repair cross-complementation group 1 (ERCC1), breast cancer 1 (BRCA1), ribonucleotide reductase M1 (RRM1) and class III ß-tubulin (TUBB3) may influence the therapeutic effect of adjuvant cisplatin-based chemotherapy. The expression of ERCC1, BRCA1, RRM1 and TUBB3 in tissues obtained from 84 patients with NSCLC was analyzed in the present non-interventional study by immunohistochemistry prior to adjuvant chemotherapy. All patients received adjuvant cisplatin-based chemotherapy. The primary endpoint in the present study was disease free survival (DFS). Out of the 84 tumors, the expression of ERCC1, BRCA1, RRM1 and TUBB3 was identified in 46 (55%), 11 (13%), 73 (87%) and 76 (90%) tissues, respectively. A beneficial response to adjuvant cisplatin-based chemotherapy in DFS was associated with the absence of the expression of ERCC1 [hazard ratio (HR), 2.166; 95% confidence interval (CI), 1.049-4.474; P=0.037] and BRCA1 (HR, 2.419; 95% CI, 1.127-5.193; P=0.023), but not with the expression status of RRM1 (HR, 0.568; 95% CI, 0.234-1.379; P=0.212) or TUBB3 (HR, 1.874; 95% CI, 0.448-7.842; P=0.39). In addition, patients lacking the expression of ERCC1 and BRCA1 benefited more from adjuvant cisplatin-based chemotherapy compared with patients that expressed either ERCC1 or BRCA1 (HR, 3.102; 95% CI, 1.343-7.163; P=0.008). The expression of ERCC1 and BRCA1 was significantly associated with the DFS time in patients with NSCLC treated with adjuvant cisplatin-based chemotherapy, respectively. The combination of the ERCC1 and BRCA1 expression levels may be a promising prognostic prediction for adjuvant cisplatin-based chemotherapy.
RESUMEN
Tyrosine-protein phosphatase non-receptor type 12 (PTPN12) has been considered to be a tumor suppressor in human cancer, but its clinical and prognostic significance in non-small cell lung cancer (NSCLC) has not been well elucidated.A retrospective analysis of 215 patients with surgically resected NSCLCs from Sun Yat-Sen University Cancer Center between April 2002 and March 2005 was performed using immunohistochemistry and Western Blot to analyze PTPN12 expression. The association between PTPN12 expression and patient survival was investigated.Western Blots showed that the expression level of PTPN12 were higher in normal paracancerous lung tissues than in NSCLC tissues. High PTPN12 expression was less common in the presence than in the absence of visceral pleural invasion (p=0.038). Patients with PTPN12-high tumors had a longer disease-free survival (DFS) (P<0.001) and overall survival (OS) (p<0.001), especially for those with non-squamous cell carcinoma (non-SCC) (DFS, p<0.001; OS, p<0.001). Multivariate analysis confirmed that PTPN12 positivity was associated with increased survival duration (DFS, p<0.001; OS, p<0.001), independent of prognostic indicator.High PTPN12 expressive levels are associated with favorable survival duration in patients with NSCLC, especially those with non-SCC. Our study suggests that PTPN12 expression is a valuable prognostic biomarker for NSCLC patients.