Correlation between BRCA1 expression and clinicopathological factors including brain metastases in patients with non-small-cell lung cancer

Abstract

Background. Previously identified as a breast and ovarian cancer susceptibility gene, BRCA1 has gained major scientific interest as a potential prognostic and/or predictive marker for various tumors, including non-small-cell lung cancer (NSCLC), the leading cause of cancer related mortality worldwide. BRCA1 plays a central role in DNA damage response (DDR. It undergoes phosphorylation by various DDR kinases at different serine residues, of which ser1524 is known to be specifically phosphorylated by ATM in response to genotoxic stress. Methods. We performed BRCA1 immunohistochemistry on several tissue microarrays (TMAs) of 113 early (I, II stage) and advanced (III, IV stage) NSCLCs, using MS110 antibody against the BRCA1 N-terminal and S1524 antibody against the phosphorylated form of BRCA1 protein at ser1524 (Abcam). Patients with III and IV stage disease were treated by adjuvant cisplatin-based chemotherapy. Staining results were correlated with overall survival (OS), disease free survival (DFS) and with the occurrence of brain metastases. Results. BRCA1 S1524 nuclear positivity was significantly correlated with longer OS and DFS in stage I and II patients (P<0.05), while OS and DFS were shorter in S1524 positive stage III and IV patients (P<0.05). No significant correlation was found with brain metastases. Conclusion.The results show that BRCA1 phosphorylaton, at least in ser1524, differentiates the fate of early and advanced NSCLC as well as response to chemotherapy, but the underlying mechanisms are not completely understood. Detection of phosphorylated forms of BRCA1 might serve as a useful prognostic and predictive marker for patients with NSCLC.

Clinical significance of breast cancer susceptibility gene 1 expression in resected non-small cell lung cancer: A meta-analysis

“…The results of the current meta-analysis which summarized 11 studies involving 1041 patients showed that positive BRCA1 expression was associated with a shorter OS and DFS without regional disparities. The conclusion was consistent with the results of the previous studies[ 18 , 21 , 25 , 26 ]. BRCA1 expression status could serve as a novel indicator for the assessment of prognosis and formulation of therapy strategy for resected NSCLC patients.…”

“…The sample sizes ranged from 32 to 221 and the proportion of patients with BRCA1 expression ranged from 13.1% to 66.7%. Furthermore, Gachechiladze et al [ 21 ] performed subgroup analysis based on the TNM stage and provided sufficient data of the two groups, so we considered them as two studies during the process of statistical analyses. Other specific information is summarized in Table 1 .…”

ATM in breast and brain tumors: a comprehensive review

“…The role of ATM in BRCA1 phosphorylation and the interaction of these proteins is established 166,167 . In addition, variants of ATM and BRCA1 have functional effects in breast cancer 141,168 .…”

“…Gachechiladze et al 166 reported a significant correlation between shorter survival and phosphorylation of BRCA1 in patients with brain metastases of lung cancer. The role of ATM in BRCA1 phosphorylation and the interaction of these proteins is established 166 , 167 . In addition, variants of ATM and BRCA1 have functional effects in breast cancer 141 , 168 .…”

Μελέτη Των Γονιδίων Του Καρκίνου Του Μαστού Και Των Ωοθηκών BRCA1 Και BRCA2 Σε Παιδιά Με Νεοπλασματικές Παθήσεις Και Στις Μητέρες Τους

“…Σε άλλη μελέτη έχει αναφερθεί ότι τόσο το BRCA1 όσο και το KRAS αποτελούν για την Ένα φαινόμενο, το οποίο δεν πρέπει να παραλείψουμε να αναφέρουμε (λόγω της μεγάλης συσχέτισής του με το γονίδιο BRCA) είναι η σχέση με την αναιμία Fanconi. Έχει διατυπωθεί από καιρό ότι η αναιμία Fanconi και η σηματοδοτική οδός του BRCA συσχετιζόμενες αφού μεταλλάξεις στο BRCA προκαλούν την παραπάνω αναιμία[103,[151][152][153]. Ταυτοχρόνως, έχει δειχθεί ότι όχι μόνο η παρουσία μεταλλάξεων στο γονίδιο Μια από τις σημαντικότερες ομάδες είναι οι DNA damage response BRCT περιοχές, οι οποίες πήραν το όνομά τους από τις περιοχές στο καρβόξυ-τελικό άκρο της πρωτεΐνης BRCA1[160][161][162][163][164][165][166][167][168][169].…”