Validation of the Genetic Signature 354849 as a Prognostic Method

Study Overview
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Brief Summary
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This prospective study is focused on the validation of the genetic signature of 27 genes as a predictor of the response to concomitant chemotherapy treatment followed by brachytherapy in patients with locally advanced cervical cancer. The genes included are: ZNF238; SAP30; C10orf137; UHRF1; SUZ12; HMGN4; RBBP4; PPP1CB; SLFN11; FLJ39378; ENDOGL1; RECQL; TRPC1; TRIO; DNAH6; GNL3L; SLC36A2; SRP9; RPE; LDOC1L; PUS7L; CCDC89; LOC644921; PLEKHG1; FAM111B; RPRD2 y ETAA16.

Detailed Description
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There are several studies of genes or genetic signatures associated with the response to treatment in cervical cancer, but so far it has not been possible to standardize the use of any biomarker or biomarker signature as a predictor of the response to treatment with reproducible results. Therefore, there is still a need to develop an effective method to predict the response to chemo-radiotherapy in locally advanced cervical cancer. This prospective study included 189 patients with cervical cancer clinical stages IB2-IVA, without previous treatment. Tumor samples will be obtained at the confirmatory diagnostic biopsy. All samples will be processed by the pathology laboratory as usual. The RNA will be extracted from the paraffin blocks with the RNeasy FFPE Kit (Qiagen) according to the manufacturer's recommendations. The RNA will be stored at -20°C until use. Quantitative PCR (qPCR) will be performed with the kit High-Capacity cDNA Reverse transcription Kit (Thermo Fisher Scientific). Primers for the 27 genes will be developed. The relative expression will be calculated using the 2- ΔΔCt method, using the expression of β-actin as a normalizing gene. In order to obtain the prognostic score, the score assigned by the classifier for the sample will be calculated from the 2-ΔΔCt values obtained for each gene. This will be done by a computer-readable medium containing the type expression profiles related to a good and a bad response to the standard treatment.

Official Title
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Prospective Study for the Validation of the Genetic Signature 354849 to Predict the Response to Standard Treatment in Patients With Locally Advanced Cervical Cancer

Conditions
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Cervix Cancer

Intervention / Treatment
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* Other: Genetic signature


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women over 18 years old Cervical Cancer at IB2-IVA FIGO´s clinical stages Histology: squamous, adenosquamous or adenocarcinoma No previous treatment No distance metastases, discard by PET/CT Functional State ECOG (Eastern Cooperative Oncology Group) 0-2 Candidates to receive standard chemoradiotherapy treatment followed by brachytherapy Exclusion Criteria: Previous chemotherapeutic, surgical and/or radiotherapy treatment for female reproductive tract pathologies Previous invasive neoplasia (except non-melanoma skin cancer) unless there is complete remission of the disease of 3 years minimum. Previous systemic chemotherapy for the current cervical cancer.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cervix cancer<br>Women older than 18 years with histopathological diagnosis of cervical cancer clinical stage I2-IVA, candidates to receive standard treatment with chemotherapy followed by brachytherapy. | Other: Genetic signature<br>* The RNA will be extracted from the tumor sample with a special kit and a q-PCR will be performed. In order to quantify the genetic expression, the comparative method called Cycle threshold or Crossing point will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Genetic signature validation | Validate the genetic signature of 27 genes to predict treatment response in patients with cervix cancer. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predictive values test | Determine sensitivity, specificity and predictive values. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genetic signature, Treatment response