Correlation Of MiR-199a-3p With Resistance To Platinum-based Chemotherapy In Gastric Cancer

Objective The correlation between mi R-199a-3p and platinum-based chemotherapy resistance in advanced gastric cancer was elucidated through functional studies of gastric cancer cells and serum specimens from gastric cancer patients,and non-invasive and early predictive biomarkers of platinum-based chemotherapy sensitivity were screened to provide a new basis for individualized treatment of gastric cancer,with the aim of improving the comprehensive diagnosis and treatment of gastric cancer.Methods Firstly,the correlation between micro RNA and gastric cancer chemoresistance was searched and analyzed by relevant literature and databases.The gastric cancer cell line MGC-803 was selected and cultured,and the drug-resistant strain MGC-803/DDP was induced.The expression quantity of mi R-199a-3p,mi R-199b-5p,mi R-133 a,mi R-133 b and mi R-34 a was further detected by q RT-PCR to screen the target micro RNA and validate them at the cellular level.Secondly,32 patients with advanced gastric cancer treated with postoperative platinum-based chemotherapy who had complete follow-up data were selected to detect mi R-199a-3p expression in preoperative patient serum by q RT-PCR and analyze the correlation between postoperative recurrence and mi R-199a-3p for further clinical level again.Results 1.Drug resistance of MGC-803/DDP was confirmed: the gastric cancer cisplatin-resistant cell line MGC-803/DDP was cultured and constructed with an IC50(Inhibitory Concentration 50)value of 47.10 ug/m L,while the IC50 value of MGC-803 cells was 14.06 ug/m L.The drug resistance index was 3.35.2.Cellular level validation: q RT-PCR was used to detect the relative expression of mi R-133 a,mi R-133 b,mi R-199a-3p,mi R-199b-5p and mi R-34 a in the parental and drug resistant strains of gastric cancer cells.In the MGC-803/DDP cell line,the expression of mi R-199a-3p was downregulated 0.52-fold(P<0.05),and the difference was statistically significant.Although there was down-regulation of mi R-199b-5p and mi R-34 a expression(P>0.05)and up-regulation of mi R-133 a and mi R-133 b expression(P>0.05),the differences were not statistically significant.Therefore,mi R-199a-3p was targeted as a target micro RNA.3.Clinical level validation: compared with postoperative platinum chemotherapy-sensitive gastric cancer patients,serum mi R-199a-3p expression levels were significantly downregulated in chemotherapy-resistant patients(P<0.05).mi R-199a-3p expression in serum of stage II gastric cancer patients was significantly higher than that of stage III gastric cancer patients(P<0.001),and serum mi R-199a-3p expression levels in patients with N1-N3 lymph node metastases were lower than those in gastric cancer patients with N0 lymph node metastases(P<0.05).And there was no correlation between the differences of serum mi R-199a-3p and age,gender,tumor size,infiltration depth,whether vascular infiltration,tumor location and tissue differentiation in gastric cancer patients(P>0.05).Conclusion mi R-199a-3p,as a noninvasive,early real-time monitoring index,can predict the sensitivity of platinum-based chemotherapy in patients with advanced gastric cancer.Meanwhile,mi R-199a-3p correlated with the progression of gastric cancer,providing a good basis for the in-depth study of the mechanism of chemotherapy resistance in gastric cancer,with the aim of improving the treatment outcome of gastric cancer.