XPG mRNA Expression Levels Modulate Prognosis in Resected Non-small-cell Lung Cancer in Conjunction With BRCA1 and ERCC1 Expression

Roberta Bartolucci; Jia Wei; Jose Javier Sanchez; Laia Perez-Roca; Imane Chaib; Francesco Puma; Raffaele Farabi; Pedro Mendez; Fausto Roila; Tatsuro Okamoto; Miquel Taron; Rafael Rosell

Disclosures

Clin Lung Cancer. 2009;10(1):47-52. 

In This Article

Results

Gene expression levels of BRCA1, ERCC1, RRM1, and XPG were detected in all tumors. Median values of each gene are shown in Table 3. ERCC1 and RRM1 expression levels were significantly higher in squamous cell carcinoma (median value: 4.41 and 2.05, respectively) than in adenocarcinoma (median value: 3.06 and 1.01, respectively; ERCC1, P = .001; RRM1, P = .02). A strong correlation was observed between these 4 genes (Table 4).

With a median follow-up of 39.1 months (range, 1-102 months), median survival time and DFS time were 51.8 months (range, 27.4-76.2 months) and 39.8 months (range, 7.7-72 months), respectively. No significant association was observed between median survival or DFS and type of surgery, histology, tumor stage, or tumor size.

Patients were subdivided into groups based on low, intermediate, and high levels of BRCA1, ERCC1, RRM1, and XPG mRNA expression (Table 5). In a univariate analysis of DFS, median DFS was not reached for patients who had low levels of BRCA1 mRNA, whereas for patients with intermediate levels, it was 17.7 months, and for patients with high levels, it was 22.4 months (P = .03; Figure 1A). Because patients with intermediate and high levels had similar DFS, these 2 groups were combined for further statistical analysis (low BRCA1 expressors [T1, lowest tercile] vs. intermediate/high BRCA1 expressors [T2, intermediate tercile/T3, highest tercile]; Table 5; Figure 1B). Median survival was not reached for patients with low BRCA1, whereas it was 40.1 months for patients with intermediate/high BRCA1 (P = .06; Table 5; Figure 1C).

Figure 1.

DFS and OS According to BRCA1 Expression
A. Disease-free survival according to BRCA1 mRNA levels by terciles. B. Disease-free survival for patients with the lowest BRCA1 mRNA levels (T1) compared with patients with intermediate (T2) and high (T3) BRCA1 mRNA levels. C. Overall survival for patients with the lowest BRCA1 mRNA levels (T1) compared with patients with intermediate (T2) and high (T3) BRCA1 mRNA levels.
Abbreviations: DFS = disease-free survival; NR = not reached; OS = overall survival

There were no significant differences in DFS or overall survival (OS) according to ERCC1, RRM1, or XPG levels. However, patients with the lowest levels of ERCC1 had better DFS (P = .09) and OS (P = .23) than patients with intermediate or high levels of ERCC1 (Table 5). Conversely, patients with the highest levels of XPG had a better DFS (P = .49) and OS (P = .21) than patients with low or intermediate levels. This seemingly discordant influence of XPG levels on survival led us to calculate the relevance of XPG in patients grouped according to low versus intermediate/high BRCA1 levels. For patients with low BRCA1, regardless of XPG mRNA expression levels, DFS was not reached. For patients with intermediate/high BRCA1 and high XPG, the DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002; Figure 2A). Similar differences were observed in OS, with median survival not reached for patients with low BRCA1, regardless of XPG levels, or for patients with intermediate/high BRCA1 and high XPG. Conversely, for patients with intermediate/high BRCA1 levels and low/intermediate XPG levels, median survival dropped to 25.5 months (P = .007; Figure 2B).

Figure 2.

DFS and OS According to BRCA1 Figure 2 and XPG Expression
A. Disease-free survival according to combination of BRCA1 and XPG levels by terciles. B. Overall survival according to combination of BRCA1 and XPG levels by terciles. Abbreviations: DFS = disease-free survival; NR = not reached; OS = overall survival; T1 = lowest tercile of mRNA expression; T2 = intermediate tercile of mRNA expression; T3 = highest tercile of mRNA expression

In the Cox regression analysis, BRCA1 and XPG mRNA levels emerged as independent prognostic factors for both median and disease-free survival (Table 6).

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