Study Of The Relationship Between Intestinal Flora And Small Cell Lung Cancer Chemotherapy Induced Diarrhea

Research Background:Small Cell Lung Cancer(SCLC)is a highly aggressive neuroendocrine tumor,which is developed rapidly,easy to occur distant metastasis in early stage,highly sensitive to chemotherapy,but easy to relapse,more than half of the patients were diagnosed at the stage of the extensive disease.According to the latest NCCN guidelines,the main treatment of SCLC is still systemic chemotherapy.Chemotherapy Induced Diarrhea(CID)is a common complication of chemotherapy,ranging from leading to a decline of the physical constitution and the quality of life of the patients,reducing patient compliance,having an impact on the efficacy of chemotherapy,increasing the cost of treatment,to causing water and electrolyte imbalance,resulting in hypovolemic shock,and then becoming life-threatening.Currently,the specific pathogenesis of CID remains unclear,studies have reported that CID is related to the change of the intestinal flora.It's of great significance for the treatment and survival of SCLC patients to explore the relationship between the change of the intestinal flora and SCLC chemotherapy induced diarrhea.Objective:To explore the relationship between small cell lung cancer chemotherapy induceddiarrhea and intestinal flora difference,and provide new strategy for the prevention and treatment of small cell lung cancer chemotherapy induced diarrhea.Method:1.Sample collection: Selecting 18 cases which were pathologically diagnosed as small cell lung cancer patients of the Second Hospital Affiliated to Dalian Medical University,and collecting their feces both before chemotherapy and after chemotherapy when the CID appears(10 patients with EP regimen,8 patients with IP regimen),then placed the feces in-80? refrigerator.2.Sample DNA extraction: Extracting the intestinal microbial genome DNA of the small cell lung cancer patients respectively,both before chemotherapy and after chemotherapy when the CID appears.3.PCR-DGGE(polymerase chain reaction-denaturing gradient gel electrophoresis): Using bacterial 16 S rDNA V3 region specific sequence as universal primers to amplify DNA samples,and the amplified product using 1.5% agarose gel electrophoresis to detect the target band,further conducting the DGGE experiment.Analysing the DGGE fingerprinting,the obviously different bands were cut down to detect the sequence and analyze the species category of the bacterium,to explore the changes of the intestinal flora of small cell lung cancer patients before chemotherapy and after chemotherapy when the CID appears.Result:1.DNA extraction: The 18 cases of SCLC patients' stool can extract the DNA,both before chemotherapy and after chemotherapy when the CID appears,the density of the DNA samples differ from high to low density.2.The characteristic of the intestinal flora of EP regimen group: By analysing the cluster analysis and principal component analysis diagram,before chemotherapy group and after chemotherapy group formed two clusters group obviously.Compared with the pre-chemotherapy group,the intestinal bacteria abundance is increased after chemotherapy(P> 0.05);diversity index is also increased(P> 0.05),both of the differences were not statistically significant.Cutting the 1,2,3 plastic bands which wereincreased the brightness significantly after chemotherapy to detect the sequence,and the result shows that the plastic band 1 and 2 may be Faecalibacterium prausnitzii,the homology is 85% and 93% respectively;plastic band 3 is Klebsiella quasipneumoniae,the homology is 99%.3.The characteristic of the intestinal flora of IP regimen group: By analysing the cluster analysis and principal component analysis diagram,before chemotherapy group and after chemotherapy group formed two clusters group obviously.Compared with the pre-chemotherapy group,the intestinal bacteria abundance is decreased after chemotherapy(P> 0.05),the difference is not statistically significant;diversity index is also decreased(P <0.05),the difference is statistically significant.Cutting the 4,5 plastic bands which were reduced the brightness significantly after chemotherapy to detect the sequence,the result shows that the plastic band 4 may be the Prevotella stercorea,the homology is 94%;the plastic band 5 may be Uncultured bacterium,the homology is81%.Conclusion:1.The difference of intestinal flora between pre-chemotherapy and after chemotherapy when CID appears of small cell lung cancer patients with EP regimen is not significant.2.Compared with the pre-chemotherapy group,the diversity index of intestinal flora of small cell lung cancer patients with IP regimen is decreased after chemotherapy when the CID appears,the difference is statistically significant.3.The small cell lung cancer patients with EP regimen may be more susceptible to infect Klebsiella quasipneumoniae in intestine,and the increased abundance of Klebsiella quasipneumoniae in intestine may be related to the small cell lung cancer Chemotherapy Induced Diarrhea with the EP regimen.