Bartolucci Roberta, Wei Jia, Sanchez Jose Javier, Perez-Roca Laia, Chaib Imane, Puma Francesco, Farabi Raffaele, Mendez Pedro, Roila Fausto, Okamoto Tatsuro, Taron Miquel, Rosell Rafael
Azienda Ospedaliera Santa Maria, Terni, Italy.
Clin Lung Cancer. 2009 Jan;10(1):47-52. doi: 10.3816/CLC.2009.n.007.
Molecular markers can help identify patients with early-stage non-small-cell lung cancer (NSCLC) with a high risk of relapse. Excision repair cross-complementing 1 (ERCC1), Xeroderma pigmentosum group G (XPG), and breast cancer 1 (BRCA1) are involved in DNA damage repair, whereas ribonucleotide reductase M1 (RRM1) is implicated in DNA synthesis. Expression levels of these molecules might therefore have a prognostic role in lung cancer.
We examined ERCC1, RRM1, XPG, and BRCA1 mRNA levels by real-time quantitative polymerase chain reaction in 54 patients with stage IB-IIB resected NSCLC. A strong correlation was observed between the 4 genes.
For patients with low BRCA1, regardless of XPG mRNA expression levels, disease-free survival (DFS) was not reached. For patients with intermediate/high BRCA1 and high XPG, DFS was 50.7 months. However, for patients with intermediate/high BRCA1 and low/intermediate XPG, DFS decreased to 16.3 months (P = .002). Similar differences were observed in overall survival, 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).
BRCA1 and XPG were identified as independent prognostic factors for both median survival and DFS. High BRCA1 mRNA expression confers poor prognosis in early NSCLC, and the combination of high BRCA1 and low XPG expression still further increases the risk of shorter survival. These findings can help optimize the customization of adjuvant chemotherapy.
分子标志物有助于识别早期非小细胞肺癌（NSCLC）复发风险高的患者。切除修复交叉互补基因1（ERCC1）、着色性干皮病G组（XPG）和乳腺癌1（BRCA1）参与DNA损伤修复，而核糖核苷酸还原酶M1（RRM1）与DNA合成有关。因此，这些分子的表达水平可能在肺癌中具有预后作用。
我们通过实时定量聚合酶链反应检测了54例IB-IIB期手术切除的NSCLC患者的ERCC1、RRM1、XPG和BRCA1 mRNA水平。观察到这4个基因之间存在强相关性。
对于BRCA1低表达的患者，无论XPG mRNA表达水平如何，均未达到无病生存期（DFS）。对于BRCA1中/高表达且XPG高表达的患者，DFS为50.7个月。然而，对于BRCA1中/高表达且XPG低/中表达的患者，DFS降至16.3个月（P = .002）。总生存期也观察到类似差异，BRCA1低表达的患者，无论XPG水平如何，或BRCA1中/高表达且XPG高表达的患者，均未达到中位生存期。相反，对于BRCA1水平中/高且XPG水平低/中的患者，中位生存期降至25.5个月（P = .007）。
BRCA1和XPG被确定为中位生存期和DFS的独立预后因素。BRCA1 mRNA高表达预示早期NSCLC预后不良，BRCA1高表达与XPG低表达相结合进一步增加了生存期缩短的风险。这些发现有助于优化辅助化疗的个体化方案。
