Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:T...Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.展开更多
Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase in...Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.展开更多
Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal ...Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.展开更多
Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mut...Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.展开更多
MicroRNA-22 (miR-22), a short non-coding RNA that post-transcriptionally regulates mRNA stability and protein synthesis, has been shown to enhance metastatic potential and to suppress HER-3, an important mRNA marker f...MicroRNA-22 (miR-22), a short non-coding RNA that post-transcriptionally regulates mRNA stability and protein synthesis, has been shown to enhance metastatic potential and to suppress HER-3, an important mRNA marker for non-small cell lung cancer (NSCLC). However, the effect of miR-22 has not been investigated in lung adenocarcinoma (LADC), the most common type of NSCLC in the Far East. In this study, we analyzed the role of miR-22 expression in LADC patients. Expression of miR-22 was detected by reverse-transcription polymerase chain reaction (RT-PCR), and confirmed by cDNA sequencing. Signals of miR-22 in LADC sections were identified using in situ hybridization (ISH). The association between miR-22 expression and survival was evaluated by the log-rank test. Induction of miR-22 expression and the effect on HER-3 levels, as well as the subsequent cell behavior were also investigated In vitro. Two types of miR-22: miR-22 and miR-22H, were detected by RT-PCR. The miR-22H had extra 13 bases, 5’-TGTGTTCAGTGGT-3’, at the 3’-end, and this segment was named miR-22E. Using ISH, miR-22E overexpression was detected in 225 (83.0%) of 271 LADC patients. A significant difference was found in cumulative survival between patients with high miR-22E levels and those with low miR-22E levels (p In vitro, epidermal growth factor induced miR-22, but reduced HER-3 expression. Expression of miR-22 increased cell movement ability. In conclusion, expression of miR-22 is closely associated with tumor recurrence, metastasis and overall survival in LADC patients by suppressing HER-3 protein expression to enhance epithelial-mesenchymal transition and metastasis.展开更多
文摘Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.
基金supported by grants from the National Natural Sciences Foundation Key Program(No.81330062)Education Ministry Innovative Research Team Program(No.IRT13003)+1 种基金Peking University-Tsinghua University Joint Center for Life Sciences Clinical Investigator,National High Technology Research and Development Program 863(No.SS2015AA020403)Beijing Technology Project(No.Z141100000214013)
文摘Background:Epidermal growth factor receptor(EGFR) mutations,including a known exon 19 deletion(19 del) and exon 21 L858 R point mutation(L858R mutation),are strong predictors of the response to EGFR tyrosine kinase inhibitor(EGFR-TKI) treatment in lung adenocarcinoma.However,whether patients carrying EGFR 19 del and L858 R mutations exhibit different responsiveness to EGFR-TKls and what are the potential mechanism for this difference remain controversial.This study aimed to investigate the clinical outcomes of EGFR-TKI treatment in patients with EGFR 19 del and L858 R mutations and explore the genetic heterogeneity of tumors with the two mutation subtypes.Methods:Of 1127 patients with advanced lung adenocarcinoma harboring EGFR 19 del or L858 R mutations,532 received EGFR-TKI treatment and were included in this study.EGFR 19 del and L858 R mutations were detected by using denaturing high-performance liquid chromatography(DHPLC).T790 M mutation,which is a common resistant mutation on exon 20 of EGFR,was detected by amplification refractory mutation system(ARMS).Next-generation sequencing(NGS) was used to explore the genetic heterogeneity of tumors with EGFR 19 del and L858 R mutations.Results:Of the 532 patients,319(60.0%) had EGFR 19 del,and 213(40.0%) had L858 R mutations.The patients with EGFR 19 del presented a significantly higher overall response rate(ORR) for EGFR-TKI treatment(55.2%vs.43.7%,P = 0.017) and had a longer progression-free survival(PFS) after first-line EGFR-TKI treatment(14.4 vs.11.4 months,P = 0.034) compared with those with L858 R mutations.However,no statistically significant difference in overall survival(OS) was observed between the two groups of patients.T790 M mutation status was analyzed in 88 patients before EGFR-TKI treatment and 134 after EGFR-TKI treatment,and there was no significant difference in the co-existence of T790 M mutation with EGFR 19 del and L858 R mutations before EGFR-TKI treatment(5.6%vs.8.8%,P = 0.554)or after treatment(24.4%vs.35.4%,P = 0.176).In addition,24 patients with EGFR 19 del and 19 with L858 R mutations were analyzed by NGS,and no significant difference in the presence of multiple somatic mutations was observed between the two genotypes.Conclusions:Patients with EGFR 19 del exhibit longer PFS and higher ORR compared with those with L858 R mutations.Whether the heterogeneity of tumors with EGFR 19 del and L858 R mutations contribute to a therapeutic response difference needs further investigation.
基金funded by National Key Scientific & Technology Support Program: Collaborative innovation of Clinical Research for chronic obstructive pulmonary disease and lung cancer (NO. 2013BAI09B09)
文摘Objective： The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor（EGFR） mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy.Patients and methods： One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin（GP） chemotherapy and second-line EGFR tyrosine kinase inhibitor（TKI） or with first-line EGFR-TKI and second-line GP chemotherapy.Results： The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups（P=0.04）. Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups（P=0.001）. Among 61 cases with thirdline pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different（P=0.001）.Conclusions： Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.
基金supported by a grant fromthe Natural Science Foundation of Xinjiang Uygur Autonomous Region(No.2021D01A24).
文摘Background:To investigate the mutation types and mutation rate of the epidermal growth factor receptor(EGFR)gene in patients with lung adenocarcinoma and the clinical features of lung adenocarcinoma with EGFR gene mutations in Karamay,Xinjiang,China.Methods:Paraffin-embedded tissue samples of adenocarcinoma patients were collected in the Karamay Central Hospital from March 2016 to June 2019,and mutations in exon 18–21 of the EGFR gene were detected by the allele-specific amplification polymerase chain reaction(Amplification RefractoryMutation System–PCR)method.The relationships between themutation types,mutation incidence,and clinical features were analyzed.Results:Of the 170 patients with lung adenocarcinoma,83 had EGFR mutations.The total mutation rate of EGFR in patients with lung adenocarcinoma was 48.8%,which included mutations in exons 18(1.2%[2/170]),19(19.4%[33/170]),20(2.4%[4/170]),and 21(20.6%[35/170]).Intriguingly,there was a case with 9 mutations in exons 20 and 21.The mutations in exon 19 of EGFR resulted in the deletion of codons 746 to 750.The main mutation in exon 21 was L858R(91.4%[32/35]).There was no significant difference in exons 19 and 21 mutation rates(P>0.05).The mutation rate of EGFR in female patients was significantly higher than that in male patients(P<0.05)but had no correlation with the age,smoking status,and clinical stage of patients with non–small cell lung cancer(P>0.05).The EGFR mutation rate may be related to the degree of tumor differentiation.Conclusions:Among patients with lung adenocarcinoma in Kelamayi(city in Xinjiang),EGFR mutations were more frequently detected in female patients,and the main sites of mutations were exons 19 and 21.
文摘MicroRNA-22 (miR-22), a short non-coding RNA that post-transcriptionally regulates mRNA stability and protein synthesis, has been shown to enhance metastatic potential and to suppress HER-3, an important mRNA marker for non-small cell lung cancer (NSCLC). However, the effect of miR-22 has not been investigated in lung adenocarcinoma (LADC), the most common type of NSCLC in the Far East. In this study, we analyzed the role of miR-22 expression in LADC patients. Expression of miR-22 was detected by reverse-transcription polymerase chain reaction (RT-PCR), and confirmed by cDNA sequencing. Signals of miR-22 in LADC sections were identified using in situ hybridization (ISH). The association between miR-22 expression and survival was evaluated by the log-rank test. Induction of miR-22 expression and the effect on HER-3 levels, as well as the subsequent cell behavior were also investigated In vitro. Two types of miR-22: miR-22 and miR-22H, were detected by RT-PCR. The miR-22H had extra 13 bases, 5’-TGTGTTCAGTGGT-3’, at the 3’-end, and this segment was named miR-22E. Using ISH, miR-22E overexpression was detected in 225 (83.0%) of 271 LADC patients. A significant difference was found in cumulative survival between patients with high miR-22E levels and those with low miR-22E levels (p In vitro, epidermal growth factor induced miR-22, but reduced HER-3 expression. Expression of miR-22 increased cell movement ability. In conclusion, expression of miR-22 is closely associated with tumor recurrence, metastasis and overall survival in LADC patients by suppressing HER-3 protein expression to enhance epithelial-mesenchymal transition and metastasis.
