RGD Reference Report - Loss of BRCA1 expression leads to worse survival in patients with gastric carcinoma. - Rat Genome Database

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Loss of BRCA1 expression leads to worse survival in patients with gastric carcinoma.

Authors: Zhang, ZZ  Liu, YJ  Yin, XL  Zhan, P  Gu, Y  Ni, XZ 
Citation: Zhang ZZ, etal., World J Gastroenterol. 2013 Mar 28;19(12):1968-74. doi: 10.3748/wjg.v19.i12.1968.
RGD ID: 9589059
Pubmed: PMID:23569343   (View Abstract at PubMed)
PMCID: PMC3613113   (View Article at PubMed Central)
DOI: DOI:10.3748/wjg.v19.i12.1968   (Journal Full-text)

AIM: To investigate the expression deficiency of key molecular markers in the homologous recombination pathway. METHODS: Expression loss of breast cancer type 1 susceptibility protein (BRCA1), ataxia telangiectasia mutated (ATM), ATM-Rad3-related (ATR), mediator of DNA damage checkpoint protein 1 (MDC1) and meiotic recombination 11 (Mre11) were correlated with their clinicopathological parameters in gastric cancer (GC). One hundred and twenty treatment-naive GC samples were formalin-fixed and paraffin-embedded into tissue blocks. Two representative cores from each block were extracted and constructed into tissue microarrays. Expression levels of BRCA1, ATM, ATR, MDC1 and Mre11 were determined using immunohistochemical analysis, and correlated with clinical parameters, including age, gender, Lauren subtype, tumor grades, clinical stage and overall survival. RESULTS: Expression loss of BRCA1, ATM, ATR, MDC1, and Mre11 was found in 21.4%, 20.2%, 21.0%, 11.1% and 4.6%, respectively, of interpretable cases. BRCA1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 8.2% vs 31.7%, P = 0.001), higher tumor grade (I/II vs III, 10.7% vs 20.5; I/II vs IV, 10.7% vs 54.5%, P = 0.047) and advanced clinical stage (I/II vs III, 12.9% vs 16.9%; I/II vs IV, 12.9% vs 45.5%, P = 0.006). MDC1 loss was significantly associated with patients of diffused subtype (intestinal vs diffused, 0% vs 19.7%, P = 0.001) and higher tumor grade (I/II vs III, 0% vs 12%; I/II vs IV, 0% vs 30.8%, P = 0.012). In addition, the survival time of the patients with expression loss of BRCA1 was significantly shorter than those with positive expression of BRCA1 (2-year survival rate, 32.4% vs 62.8%, P = 0.015). No correlations were found between clinicopathological parameters and expression loss of ATM, ATR and Mre11. CONCLUSION: Our results support the hypothesis that homologous recombination deficiency plays an important role in the progression of gastric carcinoma. Loss of expression of BRCA1 and MDC1 may serve as predictive factors in tumor development or progression in GC patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
stomach carcinoma disease_progressionIEP 9589059 RGD 
stomach carcinoma disease_progressionISOBRCA1 (Homo sapiens)9589059; 9589059 RGD 
stomach carcinoma severityIEP 9589059protein:decreased expression:stomach (human)RGD 
stomach carcinoma severityISOMDC1 (Homo sapiens)9589059; 9589059protein:decreased expression:stomach (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Brca1  (BRCA1, DNA repair associated)
Mdc1  (mediator of DNA damage checkpoint 1)

Genes (Mus musculus)
Brca1  (breast cancer 1, early onset)
Mdc1  (mediator of DNA damage checkpoint 1)

Genes (Homo sapiens)
BRCA1  (BRCA1 DNA repair associated)
MDC1  (mediator of DNA damage checkpoint 1)


Additional Information