RGD Reference Report - Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure. - Rat Genome Database

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Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure.

Authors: Balacescu, O  Balacescu, L  Tudoran, O  Todor, N  Rus, M  Buiga, R  Susman, S  Fetica, B  Pop, L  Maja, L  Visan, S  Ordeanu, C  Berindan-Neagoe, I  Nagy, V 
Citation: Balacescu O, etal., BMC Cancer. 2014 Apr 8;14:246. doi: 10.1186/1471-2407-14-246.
RGD ID: 11252104
Pubmed: PMID:24708616   (View Abstract at PubMed)
PMCID: PMC4021393   (View Article at PubMed Central)
DOI: DOI:10.1186/1471-2407-14-246   (Journal Full-text)

BACKGROUND: Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. METHODS: Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient's 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. RESULTS: A 2859-gene signature was identified to distinguish between responder and non-responder patients. 'DNA Replication, Recombination and Repair' represented one of the most important mechanisms activated in non-responsive cervical tumors, and the 'Role of BRCA1 in DNA Damage Response' was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. CONCLUSIONS: Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the patients at risk for treatment failure.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cervical squamous cell carcinoma severityIEP 11252104mRNA more ...RGD 
cervical squamous cell carcinoma severityISOBRIP1 (Homo sapiens)11252104; 11252104mRNA more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Brip1  (BRCA1 interacting helicase 1)

Genes (Mus musculus)
Brip1  (BRCA1 interacting protein C-terminal helicase 1)

Genes (Homo sapiens)
BRIP1  (BRCA1 interacting helicase 1)


Additional Information