Identification of core genes and outcomes related to the effect of Crizotinib on gastric cancer using bioinformatics analysis

Gastric cancer (GC) is a common malignant neoplasm of gastrointestinal tract. Currently, gastric cancer therapies mainly include surgery, adjuvant and palliative chemotherapy, biologic therapy, targeted therapy, and radiation therapy. However, most gastric cancer patients have missed the chance of surgery at the time of diagnosis. Traditional radiotherapy and chemotherapy are less effective and molecular targeted drugs for gastric cancer are also limited. Therefore there is a great need for screening new targets and developing and approving targeted drugs. Recent studies have shown that preoperative chemotherapy with FLOT regimens (۵-FU, leucovorin, oxaliplatin, and docetaxel without radiotherapy) are the standard treatment in the West. Two-drug chemotherapy is the best primary treatment for the metastatic disease. It is better than S-۱ monotherapy (۴), but studies on the safest drug with the least side effects and longer patient survival are still ongoing.Crizotinib is a novel drug for GC, and it is an oral small molecule inhibitor that targets both the ALK receptor tyrosine kinase (ALK) and the MET gene .It demonstrates great potential in resetting AL-ROS or proto-oncogene ۱ (ROS۱) or enhancing MET, yet its molecular mechanisms and interactions in GC treatment are largely unknown . in this study we have tried to better Identify the core genes and outcomes related to the effect of Crizotinib on gastric cancer using bioinformatics analysis and using PPI analysis. To decipher the interactions and mechanisms of the drug, we constructed a PPI network, and studied the relationships between proteins involved in the response to chemotherapy on gastric cancer tumor cells.There are few reports of this drug in patients with gastric cancer with C-MET amplification. Experiments in vitro and in vivo have shown that metastatic gastric cancer cells and MET are highly sensitive to the Crizotinib treatment. Studies have shown that network analysis based on the interplay between specific genes or proteins involved in disease and drug responsiveness is effective in identifying the major pathways and biomarkers involved in causing disease and their drug response. Given that the mechanisms of the networks responsible for the gastric cancer response to this drug have not been precisely identified, the identification of these pathways could be effective in designing future drugs with less side effects in the treatment of cancer.

Keywords:

gastric cancer , Crizotinib , PPI , MCODE subnetwork , pathway Enrichment analysis