Evidence for predictive role of BRCA1 and bTUBIII in gastric cancer

Abstract

Sensitivity of gastric cancer (GC) to conventional cytotoxic therapy may be at least in part attributed to molecular features of the tumor cells. We analyzed all patients with metastatic GC treated in the N.N. Petrov Institute of Oncology (St. Petersburg) within years 1999-2010 and identified 65 cases with evaluable treatment response and available biological material. Two of 65 patients (3 %) carried germ-line BRCA1 5382insC mutation and demonstrated particularly pronounced response to the treatment; both of their tumors showed loss of the remaining BRCA1 allele, thus confirming the causative role of BRCA1 heterozygosity in GC predisposition. RNA expression of TS, DPD, BRCA1, ERCC, TOP2A and bTUBIII was analyzed in the remaining 63 tumors. Low BRCA1 expression was associated with increased response rate [6/9 (67 %) vs. 17/54 (32 %), p = 0.04]. Low bTUBIII level correlated with the improved probability of tumor response [21/49 (43 %) vs. 1/13 (8 %), p = 0.02] and prolonged overall survival (10.5 vs. 7.1 months, p = 0.02); this trend was maintained both for taxane-containing and for taxane-free drug combinations. We conclude that GC should be considered as a part of BRCA1-related hereditary cancer syndrome. Tumors with BRCA1 inactivation and low bTUBIII expression demonstrate improved response to cytotoxic therapy.

Quantum dot-based immunofluorescent imaging and quantitative detection of TOP2A and prognostic value in triple-negative breast cancer

“…While TOP2A has been extensively studied in tumor samples, such as breast cancer, prostate cancer, gastric cancer, and ovarian cancer, [25][26][27][28] its role in carcinogenesis …”

Class III beta-tubulin, drug resistance and therapeutic approaches in cancers

“…Both overall survival (OS) and progression free survival (PFS) reached significance when surviving class III betatubulin was analyzed in combination (Gao et al, 2011). In another study in gastric cancer, inactivation of Brca1 and low class III beta-tubulin provide a better utility in predicting responses to cytotoxic therapy, regardless of taxane-containing or taxane-free drug combinations (Moiseyenko et al, 2013). In breast cancer, the double-negative expression of class III beta-tubulin and survivin responded significantly better to docetaxel and had longer PFS (p<0.05) when compared with doublepositive patients (Yuan et al, 2012).…”

Predictive biomarkers for targeted and cytotoxic agents in gastric cancer for personalized medicine

“…BRCA1 heterozygosity has been found to cause a predisposition to GC (59). A low level of BRCA1 mRNA in a tumor was associated with an increased response rate (59).…”

“…BRCA1 heterozygosity has been found to cause a predisposition to GC (59). A low level of BRCA1 mRNA in a tumor was associated with an increased response rate (59). However, conflicting results have been reported since BRCA1 levels in plasma and a tumor were positively associated with docetaxel sensitivity.…”