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BACKGROUND@#Osimertinib is approved by Food and Drug Administration for patients with advanced non-small cell lung cancer carrying EGFR-T790M mutations. Osimertinib therapy was missed in many patients who were unable to perform biopsy due to occult lesion progression or weak body. In this study. We hope that some proteins associated with predicting EGFR-T790M resistance could be screened from the serum to provide help for clinical medication. The aim of this study is to explore the protein associated with EGFR-T790M drug resistance gene and provide help for clinical medication.@*METHODS@#In this study, 36 patients with advanced lung adenocarcinoma treated by gefitinib were included. After the disease progression of the patients, biopsy was performed. 18 patients in the EGFR-T790M mutation group and 18 patients in the non-EGFR-T790M mutation group were detected by the ARMS method. Serum of patients with drug resistance was collected, and proteins related to EGFR-T790M resistance were screened by isotopic marker relative and absolute quantitative marker combined with two-dimensional liquid chromatography tandem mass spectrometry proteomics technology.@*RESULTS@#Seventeen different proteins were screened out, including 6 up-regulated proteins and 11 down-regulated proteins associated with EGFR-T790M gene mutation, which were mainly involved in 31 biological processes, 7 cell components and 26 molecular functions. Twelve enrichment pathways were identified, among which the highest enrichment index was the coagulation cascade pathway.@*CONCLUSIONS@#Seventeen proteins associated with EGFR-T790M resistance were found, and proteins involved in the coagulation cascade pathway are expected to be biomarkers associated with predicting EGFR-T790M resistance mutations.
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Objective To investigate the expressions of thymidylate synthase (TS) and methylene tetrahydrofolate reductase (MTHFR) polymorphisms and the therapeutic efficacy of chemotherapy with pemetrexed and platinum in advanced lung adenocarcinoma patients. Methods Fifty-eight patients with advanced lung adenocarcinoma were enrolled in this study. The blood samples from 25 of them were examined for extraction of DNA. The associations of the gene polymorphisms with the chemotherapy efficacy and PFS were analyzed. Results Disease control rate was noted by 38％ and the median time of progression-free survival was 8.1 months among 58 patients.There were 16％, 32％, 52％, and TS genotypes as 2R/2R, 2R/3R and 3R/3R respectively; the difference in the control rate between those with TS gene of 3R/3R and those with TS gene of R/2R+2R/3 R was significant statistically (53.8％ vs. 91.7％, P = 0.046) , but the difference in PFS was statistically insignificant (9.3 vs. 10.4 months, P> 0.05). There were 40％, 52％, 8％, and MTHFR genotypes as CC, CT and TT respectively. The DCR in those with MTHFR CC and C/T + T/T was 70％ and 73.3％, respectively and PFS was 10 months and 9.7 months respectively, showing no significant difference (P> 0.05). Conclusion The TS gene polymorphism is associated with therapeutic effect of pemetrexed for advanced lung adenocarcinoma, but MTHFR is not.
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Objective: To investigate the application of single-molecule PCR (SM-PCR) in the detection of plasma ctDNA for the treat-ment of patients with advanced lung adenocarcinoma. Methods: In total, 30 patients diagnosed with advanced lung adenocarcinoma were enrolled between June 2017 and May 2018. ctDNA fragments of the target genes (EGFR, KRAS, BRAF, ALK, HER2, and TP53) from the blood samples were enriched by SM-PCR, and DNA libraries were prepared. Finally, a high-throughput sequencing was performed. The EGFR detection of tumor tissue samples was performed using real-time fluorescence PCR based on the amplification refractory mutation system (ARMS) and consistency in the results of EGFR mutation detection in the plasma and tissue was compared. Results:The results of both the methods were consistent (Kappa=0.867, P<0.001). The McNemar's test also indicated that the results are not statistically different (P=0.500). Conclusions: SM-PCR can be used for the detection of plasma EGFR mutations. The target detection sites are more comprehensive and multiple mutations can be detected at the same time. Results of the analysis are more precise and can be absolutely quantified.
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OBJECTIVE:To observe therapeutic efficacy and safety of hyperthermia combined with pemetrexed and cisplatin for medium and advanced lung adenocarcinoma. METHODS:Medical information of 120 patients with medium and advanced lung ade-nocarcinoma were analyzed retrospectively. They were divided into control group(60 cases)and observation group(60 cases)ac-cording to therapy method. Control group was given Pemetrexed disodium for injection 500 mg/m2 intravenously,d1+Cisplatin for injection 75 mg/m2 intravenously,d2-4. A treatment course lasted for 21 d,and both received 2 courses of treatment at least. Obser-vation group was additionally given hyperthermia,once a month,2-4 times in total,on the basis of control group. Clinical effica-cies,the improvement of life quality and the occurrence of toxic reaction were observed in 2 groups. RESULTS:Both groups re-ceived 2 courses of treatment at least. Total response rate of observation group(63.3%)was significantly higher than that of con-trol group(36.7%),and the improvement rate of life quality(60.0%)was significantly higher than control group(33.3%),with statistical significance (P<0.05). There was no statistical significance in Ⅲ-Ⅳ degree liver and renal function injury,myelosup-pression or the incidence of gastrointestinal tract between 2 groups (P>0.05). CONCLUSIONS: Hyperthermia combined with pemetrexed and cisplatin shows significant therapeutic efficacy for medium and advanced lung adenocarcinoma and improves surviv-al quality without increasing the occurrence of toxic reaction.