Expression Profile And Bioinformatics Analysis And Related Functions Of Circ Rna Microarray In Patients With Advanced Gastric Cancer With Platinum-Containing Chemotherapy

Gastric cancer?GC?is the fourth common malignant tumor and the second leading cause of death in patients with malignant tumors in the world.Although the treatment of tumors continues to develop and improve,the prognosis of advanced gastric cancer remains poor.At present,platinum-based combination chemotherapy is still the first-line treatment option for advanced gastric cancer,and chemotherapy resistance is often the main cause of chemotherapy failure.Therefore,finding molecular markers that can predict the efficacy of platinum-based chemotherapy in patients with gastric cancer can provide a theoretical basis for individualized treatment of gastric cancer.Circular RNA?circ RNA?is a special type of non-coding RNA,which has gradually become a research hotspot in recent years.Related studies at home and abroad have shown that circ RNA could be involved in the regulation of tumorigenesis,development and chemoresistance.Based on these literatures,our study aims to explore the circ RNA and its related biological functions and clinical significance related to platinum-based chemotherapy resistance in gastric cancer.This study contains two parts.Part 1 Expression profile and bioinformatics analysis of plasma differentially expressed circular RNA in patients with advanced gastric cancer undergoing platinum-containing chemotherapyAim Using circ RNA microarray technology,plasma differentially expressed circ RNAs were screened to predict the efficacy of platinum-containing chemotherapy in patients with advanced gastric cancer,and bioinformatics analysis was performed to lay the foundation for further research on circ RNA as a biomarker to predict the efficacy of gastric cancer chemotherapy.Methods1.Collecting patients with advanced gastric cancer who have been newly diagnosed and treated with cisplatin or oxaliplatin for at least 2 courses.The peripheral blood of these patients was taken before the initial chemotherapy,and the plasma was separated by centrifugation and stored in a refrigerator at-80 ° C for circ RNA microarray.According to the solid tumor efficacy evaluation criteria RECIST1.1,the chemotherapy efficacy of gastric cancer patients was evaluated and the patients were divided into the chemotherapy sensitive group and resistant group.2.CircRNA microarray was used to detect the circRNA expression in plasma of patients with advanced gastric cancer in the platinum-containing chemotherapy sensitive group and the resistant group.And the circ RNA-mi RNA co-expression network was constructed using mi Randa software to predict circ RNA that the mi RNA may bind to.Then Disease,GO?Gene Ontology?and pathway enrichment analysis were used to predict the biological function of the differentially expressed circ RNA corresponding to the linear transcript and the signaling pathways involved.Results1.Compared with the chemotherapy sensitive group,circ RNA microarray detected181 differentially expressed circ RNAs in the chemotherapy resistant group,of which173 were up-regulated and 8 were down-regulated?FC? 2?.2.Through mi Randa software,it was found that circRNA may participate in the regulation of chemosensitivity through mi RNA sponge.And bioinformatics analysisrevealed that dysregulated circ RNA-derived m RNA may be involved in chemosensitivity-related signaling pathways,such as Hippo signal pathway,focal adhesion spot,MAPK signal pathway and so on.Conclusion Differentially expressed circ RNAs related to the efficacy of platinum-containing chemotherapy for advanced gastric cancer were screened and its biological functions were identified,which are helpful to elucidate the molecular mechanism of platinum-containing chemotherapy sensitivity or resistance in gastric cancer patients,and provide a reference for clinical patients with advanced gastric cancer to choose platinum-containing chemotherapy.Part 2 The effects of hsa_circ₀010985 on the drug sensitivity and biological functions of gastric cancer cells and its clinical significanceAim To study the expression of hsa_circ₀010985 in gastric cancer cells and tissues,and explore the effects of hsa_circ₀010985 expression on the drug sensitivity ?proliferation and apoptosis of GC cells and its clinical significance.Methods q RT-PCR was performed to detect the expression level of hsa_circ₀010985 in GC cells and tissues.And the relationship between the expression level of hsa_circ₀010985 and the clinicopathological parameters of GC patients was analyzed.A receiver operating characteristic?ROC?curve was used to evaluate the diagnostic value of hsa_circ₀010985.SGC7901/DDP and BGC-823 cells were transfected with si RNA to knockdown hsa_circ₀010985 expression.And then,drugsensitivity?cell proliferation and apoptosis were detected by CCK8 and AV/PI assays.Results Hsa_circ₀010985 was highly expressed in SGC7901/DDP compared to SGC7901 cells,and was highly expressed in GC cells compared to GES-1 cells.The expression level in GC tissues was significantly higher than that in normal gastric mucosa tissues,all the differences were statistically significant?P < 0.05?.There were statistically significant differences between the hsa_circ₀010985 expression level and lymph node metastasis?P < 0.05?,but no statistically significant differences between the expression level and gender,age,tumor diameter,TNM stage,CEA,CA199?ca-199?,and tumor location?P > 0.05?.The area under the ROC curve?AUC?was 0.631?P <0.05?and the specificity and sensitivity were 0.814 and 0.419,respectively,suggesting that it may have certain reference value for the diagnosis of GC.Knockdown of hsa_circ₀010985 can reduce the viability of SGC7901/DDP to some extent,reverse cisplatin resistance,and promote the decreased proliferation capacity and increased apoptosis rate of GC cells.Conclusion Hsa_circ₀010985 may promote cisplatin resistance in gastric cancer,promote the development of GC cells,and is expected to be a biomarker for GC diagnosis and therapeutic target.