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G/GEJ adenocarcinoma is one of the most common malignant tumors in China, ranking the fifth highest incidence and third highest mortality worldwide. Currently, surgical resection is the preferred treatment for G/GEJ adenocarcinoma, while the 5-year survival rate of patients is lower than 25%. Compared with surgical resection, immunotherapy is proved to be able to effectively prolong the survival time of patients. On one hand, with the continuous promotion of immunotherapy drugs, the exploration of neoadjuvant application of immunotherapy in G/GEJ adenocarcinoma has become a hotspot in recent years. It's also on their way that clinical trials of programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1) and other immune checkpoints are carried out. On the other hand, the research found that although the curative effect of immune therapy seems better, the present G/GEJ adenocarcinoma immunotherapy marker researches mainly focused on the late stage of the cancer, with few studies of immune markers of neoadjuvant therapy for G/GEJ adenocarcinoma. Additionally, it's not quite feasible for single biomarkers to predict the immune treatment effect precisely. Therefore, combined with clinicopathology and therapeutic effects, this study is aimed to construct the efficacy prediction model of anti-PD-1 antibody together with chemotherapy for G/GEJ adenocarcinoma, by detecting RNA expression. Furthermore, this study will perform drug sensitivity test and bio-molecular test on patient derived organoid model to validate the biomarkers found from biological specimens.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PD-1 group | Patients who are qualified for receiving anti-PD-1 antibody combined with chemotherapy neoadjuvant therapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DNA panel and RNA Sequencing | Other | Interventions include collecting samples, DNA panel test and full transcriptome sequencing. Before collecting samples, obtaining written informed consent from patient in advance.
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| Measure | Description | Time Frame |
|---|---|---|
| Relative RNA biomarkers | At the RNA level, to identify the biomarkers related to the efficacy of neoadjuvant therapy with PD-1 mab combined with chemotherapy in locally advanced gastric cancer. | From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years |
| Prediction model for efficacy | A prediction model for the efficacy of PD-1 mab combined with chemotherapy, constructed on the basis of clinical pathology, gene variation, gene expression and other factors. | From the date of completing collecting data, to the date of death from any cause or the end date of the whole trail, whichever came first, assessed up to 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Conditions of immune microenvironment | To monitor the changes of immune microenvironment before and after neoadjuvant treatment with PD-1 mab combined with chemotherapy for locally advanced gastric cancer. To evaluate whether the tumor infiltration immune cell and organoid co-cultural system can rebuild the tumor immune micro-environment, the immune cell subpopulations will be detected by single-cell sequencing, immunofluorescence staining and flow-cytometry. |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with G/GEJ adenocarcinoma who are ready to receive PD-1 monoclonal antibody combined with chemotherapy neoadjuvant treatment.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Xijing Hospital of Digestive Diseases | Xi'an | Shaanxi | 710000 | China |
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| ID | Term |
|---|---|
| D017423 | Sequence Analysis, RNA |
| ID | Term |
|---|---|
| D017421 | Sequence Analysis |
| D005821 | Genetic Techniques |
| D008919 | Investigative Techniques |
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Biological samples of DNA will be collected before and after neoadjuvant treatment with PD-1 mab combined with chemotherapy, then they will be used to detect and analyze the variation in DNA. Biological samples of RNA detection will be used to analyze the expression profile. Combined with clinicopathological features, clinical treatment efficacy and prognosis, samples of DNA and RNA will be used to analyze biomarkers and construct models for predicting efficacy of PD-1 mab combined with chemotherapy in locally advanced gastric cancer. Meanwhile, the investigators are going to establish organoids with immune microenvironment from surgically resected tumor tissues of G/GEJ adenocarcinoma patients. Organoids will be treated with the same immune-chemotherapy drugs with the corresponding patients who accepted neoadjuvant therapy.
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| From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years |
| Drug resistance mechanism | To explore the drug resistance mechanism of locally advanced gastric cancer after neoadjuvant therapy with PD-1 mab combined with chemotherapy. | From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years |
| Response of organoids to the same neoadjuvant drugs as the corresponding patients | The investigators will establish the G/GEJ adenocarcinoma organoid and tumor infiltration immune cell co-cultural model. The model will be treated with the same PD-1 mab combined with chemotherapy drugs as the corresponding patients. The viability of the organoids will be observed and quantified after treatment. The correlation of 3D organoid sensitivity and the patient response will be analyzed. And RNA expression detection of organoids before and after treatment will be performed to further validate the biomarkers from biological specimens. | From the initiation date of patients recruited into groups to the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years |