Neoplasms

All Conditions

Adenocarcinoma

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Tislelizumab

Immunoglobulins

Patients who are qualified for receiving anti-PD-1 antibody combined with chemotherapy neoadjuvant therapy

Interventions include collecting samples, DNA panel test and full transcriptome sequencing.

Before collecting samples, obtaining written informed consent from patient in advance.

1. Blood cell samples;
2. Paraffin sample of residual tumor tissue of biopsy;
3. Paraffin sample of residual tumor tissue and paracancer tissue after gastrectomy.

DNA panel and RNA Sequencing

Gang Ji, Doctoral

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.

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.

Biomarker Analysis of Tislelizumab Combined With Chemotherapy for Perioperative Treatment of G/GEJ Adenocarcinoma

Predictive Biomarker Analysis and Model Construction of Tislelizumab Combined With Chemotherapy for Perioperative Treatment of G/GEJ Adenocarcinoma: A Single-center, Observational Study

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.

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.

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.

To explore the drug resistance mechanism of locally advanced gastric cancer after neoadjuvant therapy with PD-1 mab combined with chemotherapy.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Biomarker Analysis of Tislelizumab Combined With Chemotherapy for Perioperative Treatment of G/GEJ Adenocarcinoma	NCT05508399	Locally Advance... PD-1	DNA panel and R...	18 Years - 80 Years	Xijing Hospital
Biomarker Analysis of Tislelizumab Combined With Chemotherapy for Perioperative Treatment of G/GEJ Adenocarcinoma	NCT05508399	Locally Advance... PD-1	DNA panel and R...	18 Years - 80 Years	Xijing Hospital

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