Objective:To investigate the antibiotic resistance genes inserted into class I and class 2integrons in Acinetobacler baumannii[A.baumannii)isolates obtained from nine different cities in Turkey.Methods:A collection of...Objective:To investigate the antibiotic resistance genes inserted into class I and class 2integrons in Acinetobacler baumannii[A.baumannii)isolates obtained from nine different cities in Turkey.Methods:A collection of 281 A.baumannii clinical isolates were collected from nine diferenl state hospitals in Turkey and were confirmed as A.baumannU by conventional biochemical,API testing and bla_(-OXA-51)specific PCR.The isolates were examined by PCR for existence of class I and2 integron gene cassettes.Results:They were characterized by antimicrobial susceptibility testing and the highest resistance rates were determined for piperacillin(90.03%),ciprofloxacin(87.54%),cefepime and trimethoprim/sulfamethoxazole(81.13%).The lowest resistance rates was for cefotaxime(3.55%).class 1 integrons were detected in 6.4%(18/281)of A.baumannii strains and no class 2 integron was detected.The gene casselles of class 1 inlegrons AacCI-AAC(3)l-aadAI,AacCI-aadA1,AAC(3)-I,AAC(3)-I-AAC(3)-I-aadA1,TEM-1.AAC(3)-I-aadA1-AAC(3)-I-AAC(3)-I,AAC(3)-I-AAC(3)-I-AAC(3)-I-aadA1,AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I,AAC(3)-I-aadA1-AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I-aadA1-AAC(3)-I-aadA1 were detected in eighteen strains.The aac genes family were most frequently found integrated into the class 1 inlegrons and it was followed by aadA genes and TEM-1 genes.Conclusions:This is an extensive study on the distribulion of class 1 integron among A.baumannii in Turkey.In addition to these,two new alleles were observed.Their percentage rates of similarity to other cassettes are 95%aadA1(TK A18)and 89%,aadA 1(ANKA3).展开更多
The class 1 integron and complex gene cassettes among different species of clinical isolates in northern China were characterized in this study. 383 clinical isolates were obtained from northern China, and class 1 int...The class 1 integron and complex gene cassettes among different species of clinical isolates in northern China were characterized in this study. 383 clinical isolates were obtained from northern China, and class 1 integrons containing gene cassettes widely distributed among gram negative clinical isolates was observed. We find that the class 1 integron showed positive correlation with multidrug resistance phenotype of gram negative bacteria. In addition, we find that isolates belonged to one species harbored different types of gene cassette arrays, while same types of gene cassette arrays were observed in different species of isolates. The diversity of gene cassette arrays among the isolates indicated the complexity of multidrug resistance in clinical isolates in northern China.展开更多
Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integro...Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integrons and antibiotic susceptibility of clinical isolates of P. aeruginosa. Two hundred and five P. aeruginosa strains were collected from the seven general state hospitals in Turkey. They were characterized by antimicrobial susceptibility testing, screened for class 1 and class 2 integrons, and evaluated for the association between antibiotic resistance phenotypes and the presence of integrons. intI gene was amplified in 10 isolates (4.87%) by PCR and in seven isolates of them (70%) were found different gene cassettes. The aadA gene integrated into the class 1 integrons was most frequently found and it was followed by aac genes and blaOXA family genes. Sequence analysis of variable regions of the class 1 integrons showed five gene cassette arrays;aadA1(99%), aac(3)-Id(82%)-orf-aac(3”)-Ia(99%), aac(3)-Ie(83%)-blaoxa10(100%)- aadA1 (100%), aadA6(99%, 100%), aac(6’)-I(97%)-orf-aadA2(99%). No class 2 integron was detected. This study is the first multicenter study for class 1 integrons and it indicates the low rate of presence of class 1 gene cassette in P. aeruginosa.展开更多
Class 1 integrons facilitate horizontal gene transfer,significantly influencing antibiotic resistance gene(ARG)dissemination within microbial communities.Wastewater treatment plants(WWTPs)are critical reservoirs of AR...Class 1 integrons facilitate horizontal gene transfer,significantly influencing antibiotic resistance gene(ARG)dissemination within microbial communities.Wastewater treatment plants(WWTPs)are critical reservoirs of ARGs and integrons,yet the integron-mediated dynamics of ARG transfer across different WWTP types remain poorly understood.Here we show distinct ARG profiles associated with class 1 integrons in municipal and industrial WWTPs using a novel approach combining nested-like highthroughput q PCR and Pac Bio sequencing.Although industrial WWTPs contained higher absolute integron abundances,their relative ARG content was lower(1.27×10^(7)–9.59×10^(7) copies per ng integron)compared to municipal WWTPs(3.72×10^(7)–1.98×10^(8) copies per ng integron).Of the 132,084 coding sequences detected from integrons,56.8%encoded antibiotic resistance,with industrial plants showing lower ARG proportions,reduced ARG array diversity,and greater incorporation of non-ARG sequences.These findings suggest industrial WWTP integrons integrate a broader array of exogenous genes,reflecting adaptation to complex wastewater compositions.This work enhances our understanding of integron-driven ARG dynamics in wastewater and offers a robust strategy for environmental integron analysis.展开更多
Class 1 integrons are vital mobile genetic elements involved in the environmental transmission of antibiotic resistance genes(ARGs).However,knowledge about the diversity and abundance of class 1 integrons and gene cas...Class 1 integrons are vital mobile genetic elements involved in the environmental transmission of antibiotic resistance genes(ARGs).However,knowledge about the diversity and abundance of class 1 integrons and gene cassettes during drinking water treatment and distribution is still limited.In this study,we aimed to uncover the prevalence of class 1 integrons in the drinking water treatment and distribution systems with the combination of culture-dependent and culture-independent methods.Further,we applied the nanopore sequencing method to characterize the diversity and arrangement of ARGs carried by class 1 integron-associated gene cassettes.A total of 42 isolates were inti-positive among the 208 strains isolated from drinking water,which tended to confer multi-drug resistance compared with intll-negative isolates.The absolute abundance of the intl1 average i.15×10^(9) copies/L in the source water and underwent the most significant reduction of over 99.9% after liquid chiorine disinfection.Furthermore,nanopore sequencing revealed that the class 1 integron-associated gene cassettes carried 51 subtypes of ARGs in drinking water,mainly conferring resistance to aminoglycosides and trimethoprim.The treatment processes,especially liquid chlorine disinfection,reduced most of the ARGs carried by gene cassettes,though some of the ARG subtypes persisted along the treatment and distribution ike aac(6)-Il,aadA,and dfrB2.The antibiotic resistance gene cassette array laac(6')-Ⅱ arr was most frequently detected,especially in the chlorinated water.This study underlined that drinking water was potential reservoir for integron-mediated ARGs transfer,indicating that the health risks of resistance gene cassettes in class 1 integrons deserved urgent attention.展开更多
Aim To determine cephalometrically the mechanism of the treatment effects of non-extraction and multiloop edgewise archwire （MEAW） technique on postpeak Class Ⅱ Division 1 patients. Methodology In this retrospectiv...Aim To determine cephalometrically the mechanism of the treatment effects of non-extraction and multiloop edgewise archwire （MEAW） technique on postpeak Class Ⅱ Division 1 patients. Methodology In this retrospective study, 16 postpeak Class Ⅱ Division 1 patients successfully corrected using a non-extraction and MEAW technique were cephalometrically evaluated and compared with 16 matched control subjects treated using an extraction technique. Using CorelDRAW software, standardized digital cephalograms preand post-active treatments were traced and a reference grid was set up. The superimpositions were based on the cranial base, the mandibular and the maxilla regions,and skeletal and dental changes were measured. Changes following treatment were evaluated using the paired-sample t-test. Student＇s t-test for unpaired samples was used to assess the differences in changes between the MEAW and the extraction control groups. Results The correction of the molar relationships comprised 54% skeletal change （mainly the advancement of the mandible） and 46% dental change. Correction of the anterior teeth relationships comprised 30% skeletal change and 70% dental change. Conclusion The MEAW technique can produce the desired vertical and sagittal movement of the tooth segment and then effectively stimulate mandibular advancement by utilizing the residual growth potential of the condyle.展开更多
Background Many cases of ClassⅡdeformities have been reported to be treated with prefabricated appliances.The aim of this study was to distinguish the clinical effect of traditional custom-made appliances and prefabr...Background Many cases of ClassⅡdeformities have been reported to be treated with prefabricated appliances.The aim of this study was to distinguish the clinical effect of traditional custom-made appliances and prefabricated appliances in the treatment of ClassⅡdivision 1 malocclusion.Therefore,soft and hard tissue changes following treatment of ClassⅡdivision 1 malocclusion using the twin-block(TB)appliance was compared to that using the Myofunctional Research Company(MRC)appliance(K1+K2)combined with oral myofunctional treatment(OMT)(MRC+OMT).Methods The study included 22 children(6 boys and 16 girls aged 9–11 years)with ClassⅡdivision 1 malocclusion along with mandibular retrognathism with a 5–12 mm overjet,basic normal maxillary status,and stage 2 or 3 cervical vertebral maturation(CVM).Participants were randomly assigned into two groups,the TB group and the MRC+OMT group for 12 months.Standardized lateral cephalograms were used to assess skeletal,dental,and soft tissue changes from pre-to post-treatment.Independent t-tests were used to compare the initial and final cephalometric status and tissue changes between the groups.Results The TB and MRC+OMT groups resulted in different degrees of lateral changes;however,improvements of skeletal and soft tissue indices were significantly greater in the TB group than in the MRC+OMT group.Conclusion TB was more effective than MRC+OMT in treating children aged 9–11 years with ClassⅡdivision 1 malocclusion.However,further research using custom-made appliances with OMT is recommended,and further investigations are needed to confirm these findings.展开更多
AIM To assess the long-term prognostic value of vascular endothelial growth factor receptor 1(VEGFR1)and classⅢβ-tubulin(TUBB3)mRNA expression in nonmetastatic rectal cancer.METHODS A total of 75 consecutive patient...AIM To assess the long-term prognostic value of vascular endothelial growth factor receptor 1(VEGFR1)and classⅢβ-tubulin(TUBB3)mRNA expression in nonmetastatic rectal cancer.METHODS A total of 75 consecutive patients with non-metastatic rectal cancer from March 2004 to November 2008 were analyzed retrospectively at our institute.The mRNA expressions of VEGFR1 and TUBB3 were detected by multiplex branched DNA liquid-chip technology.The Cutoff Finder application was applied to determine cutoff point of mRNA expression.SPSS software version 22.0was used for analysis.RESULTS The median follow-up was 102.7 mo(range,6-153.6).Theχ~2 and Fisher’s exact tests showed that VEGFR1expression was related to lymph node metastasis(P=0.013),while no relationships between TUBB3 and clinicopathological features were observed.Univariate analysis showed that T stage,lymph node metastasis,tumor differentiation,VEGFR1 and TUBB3 mRNA expression were correlated to overall survival(OS)(P=0.048,P=0.003,P=0.052,P=0.003 and P=0.015,respectively).Also,lymph node metastasis and VEGFR1expression independently influenced OS by multivariate analysis(P=0.027 and P=0.033).VEGFR1 expression was positively correlated with TUBB3(P=0.024).The patients with low expression of both TUBB3 and VEGFR1 presented a better OS(P=0.003).In addition,the receiver operating characteristic analysis suggested that the combination of lymph node metastasis and VEGFR1 had a more favorable prognostic value(P<0.001).CONCLUSION VEGFR1 expression and lymph node metastasis independently and jointly affect survival.Moreover,low expression of VEGFR1 and TUBB3 presented a better OS in patients with non-metastatic rectal cancer,which might serve as a potential prognostic factor.展开更多
BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully unde...BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.AIM To investigate the roles and mechanisms of SERPINB5 in rectal cancer.METHODS SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis.SW480 cells were transfected with pcDNASERPINB5 or short-hairpin RNA targeting SERPINB5(sh-SERPINB5).Cell proliferation,invasion,and apoptosis were then evaluated.The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1(HSP90AA1)was confirmed through a co-immunoprecipitation assay.Subsequently,pcDNAHSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells,and cell progression was then detected.Moreover,rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression.Additionally,sh-SERPINB5-transfected SW480 cells were implanted into nude mice,and xenograft tumor growth was then evaluated.RESULTS SERPINB5 was prominently upregulated in rectal cancer tissues and cells.SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis.In contrast,SERPINB5 knockdown had the opposite effects.Moreover,SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells.HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis.By contrast,HSP90AA1 knockdown suppressed cell progression.The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression.Additionally,SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.CONCLUSION SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.展开更多
基金Supported by Recep Tayyip Erdogan University(Grant No.BAP2012.102.03.4.and BAP-2013.102.03.4)
文摘Objective:To investigate the antibiotic resistance genes inserted into class I and class 2integrons in Acinetobacler baumannii[A.baumannii)isolates obtained from nine different cities in Turkey.Methods:A collection of 281 A.baumannii clinical isolates were collected from nine diferenl state hospitals in Turkey and were confirmed as A.baumannU by conventional biochemical,API testing and bla_(-OXA-51)specific PCR.The isolates were examined by PCR for existence of class I and2 integron gene cassettes.Results:They were characterized by antimicrobial susceptibility testing and the highest resistance rates were determined for piperacillin(90.03%),ciprofloxacin(87.54%),cefepime and trimethoprim/sulfamethoxazole(81.13%).The lowest resistance rates was for cefotaxime(3.55%).class 1 integrons were detected in 6.4%(18/281)of A.baumannii strains and no class 2 integron was detected.The gene casselles of class 1 inlegrons AacCI-AAC(3)l-aadAI,AacCI-aadA1,AAC(3)-I,AAC(3)-I-AAC(3)-I-aadA1,TEM-1.AAC(3)-I-aadA1-AAC(3)-I-AAC(3)-I,AAC(3)-I-AAC(3)-I-AAC(3)-I-aadA1,AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I,AAC(3)-I-aadA1-AAC(3)-I-aadA1,AAC(3)-I-AAC(3)-I-aadA1-AAC(3)-I-aadA1 were detected in eighteen strains.The aac genes family were most frequently found integrated into the class 1 inlegrons and it was followed by aadA genes and TEM-1 genes.Conclusions:This is an extensive study on the distribulion of class 1 integron among A.baumannii in Turkey.In addition to these,two new alleles were observed.Their percentage rates of similarity to other cassettes are 95%aadA1(TK A18)and 89%,aadA 1(ANKA3).
基金supported by Twelfth Five-Year Mega Project of Research on The Prevention and Control of HIV/AIDS,Viral Hepatitis Infectious Diseases 2013ZX10004-217 from the Ministry of Science and Technology,People’s Republic of China,the Project Sponsored by the Young Scholar Scientific Research Foundation of China CDC(No.2013A101)General Program of State Key Laboratory for Infections Disease Prevention and Control(No.2012SKLID205)
文摘The class 1 integron and complex gene cassettes among different species of clinical isolates in northern China were characterized in this study. 383 clinical isolates were obtained from northern China, and class 1 integrons containing gene cassettes widely distributed among gram negative clinical isolates was observed. We find that the class 1 integron showed positive correlation with multidrug resistance phenotype of gram negative bacteria. In addition, we find that isolates belonged to one species harbored different types of gene cassette arrays, while same types of gene cassette arrays were observed in different species of isolates. The diversity of gene cassette arrays among the isolates indicated the complexity of multidrug resistance in clinical isolates in northern China.
基金supported by Recep Tayyip Erdogan University Research Fund Grants BAP-2013.102.03.12 and BAP-2013.102.03.13.
文摘Pseudomonas aeruginosa is one of the leading nosocomial pathogens worldwide, and their infections are difficult to treat due to acquired resistance to many antibiotics. This study aimed to detect class 1 and 2 integrons and antibiotic susceptibility of clinical isolates of P. aeruginosa. Two hundred and five P. aeruginosa strains were collected from the seven general state hospitals in Turkey. They were characterized by antimicrobial susceptibility testing, screened for class 1 and class 2 integrons, and evaluated for the association between antibiotic resistance phenotypes and the presence of integrons. intI gene was amplified in 10 isolates (4.87%) by PCR and in seven isolates of them (70%) were found different gene cassettes. The aadA gene integrated into the class 1 integrons was most frequently found and it was followed by aac genes and blaOXA family genes. Sequence analysis of variable regions of the class 1 integrons showed five gene cassette arrays;aadA1(99%), aac(3)-Id(82%)-orf-aac(3”)-Ia(99%), aac(3)-Ie(83%)-blaoxa10(100%)- aadA1 (100%), aadA6(99%, 100%), aac(6’)-I(97%)-orf-aadA2(99%). No class 2 integron was detected. This study is the first multicenter study for class 1 integrons and it indicates the low rate of presence of class 1 gene cassette in P. aeruginosa.
基金National Natural Science Foundation of China(No.51938001,51708253,and 52300243)National Key Research and Development Program of China(2023YFC3207004)。
文摘Class 1 integrons facilitate horizontal gene transfer,significantly influencing antibiotic resistance gene(ARG)dissemination within microbial communities.Wastewater treatment plants(WWTPs)are critical reservoirs of ARGs and integrons,yet the integron-mediated dynamics of ARG transfer across different WWTP types remain poorly understood.Here we show distinct ARG profiles associated with class 1 integrons in municipal and industrial WWTPs using a novel approach combining nested-like highthroughput q PCR and Pac Bio sequencing.Although industrial WWTPs contained higher absolute integron abundances,their relative ARG content was lower(1.27×10^(7)–9.59×10^(7) copies per ng integron)compared to municipal WWTPs(3.72×10^(7)–1.98×10^(8) copies per ng integron).Of the 132,084 coding sequences detected from integrons,56.8%encoded antibiotic resistance,with industrial plants showing lower ARG proportions,reduced ARG array diversity,and greater incorporation of non-ARG sequences.These findings suggest industrial WWTP integrons integrate a broader array of exogenous genes,reflecting adaptation to complex wastewater compositions.This work enhances our understanding of integron-driven ARG dynamics in wastewater and offers a robust strategy for environmental integron analysis.
基金financially supported by the National Natural Science Foundation of China(Nos.52025102,52192682,and 52200057)the Jiangsu Funding Program for Excellent Postdoctoral Talent(China)(No.2022ZB35).
文摘Class 1 integrons are vital mobile genetic elements involved in the environmental transmission of antibiotic resistance genes(ARGs).However,knowledge about the diversity and abundance of class 1 integrons and gene cassettes during drinking water treatment and distribution is still limited.In this study,we aimed to uncover the prevalence of class 1 integrons in the drinking water treatment and distribution systems with the combination of culture-dependent and culture-independent methods.Further,we applied the nanopore sequencing method to characterize the diversity and arrangement of ARGs carried by class 1 integron-associated gene cassettes.A total of 42 isolates were inti-positive among the 208 strains isolated from drinking water,which tended to confer multi-drug resistance compared with intll-negative isolates.The absolute abundance of the intl1 average i.15×10^(9) copies/L in the source water and underwent the most significant reduction of over 99.9% after liquid chiorine disinfection.Furthermore,nanopore sequencing revealed that the class 1 integron-associated gene cassettes carried 51 subtypes of ARGs in drinking water,mainly conferring resistance to aminoglycosides and trimethoprim.The treatment processes,especially liquid chlorine disinfection,reduced most of the ARGs carried by gene cassettes,though some of the ARG subtypes persisted along the treatment and distribution ike aac(6)-Il,aadA,and dfrB2.The antibiotic resistance gene cassette array laac(6')-Ⅱ arr was most frequently detected,especially in the chlorinated water.This study underlined that drinking water was potential reservoir for integron-mediated ARGs transfer,indicating that the health risks of resistance gene cassettes in class 1 integrons deserved urgent attention.
文摘Aim To determine cephalometrically the mechanism of the treatment effects of non-extraction and multiloop edgewise archwire （MEAW） technique on postpeak Class Ⅱ Division 1 patients. Methodology In this retrospective study, 16 postpeak Class Ⅱ Division 1 patients successfully corrected using a non-extraction and MEAW technique were cephalometrically evaluated and compared with 16 matched control subjects treated using an extraction technique. Using CorelDRAW software, standardized digital cephalograms preand post-active treatments were traced and a reference grid was set up. The superimpositions were based on the cranial base, the mandibular and the maxilla regions,and skeletal and dental changes were measured. Changes following treatment were evaluated using the paired-sample t-test. Student＇s t-test for unpaired samples was used to assess the differences in changes between the MEAW and the extraction control groups. Results The correction of the molar relationships comprised 54% skeletal change （mainly the advancement of the mandible） and 46% dental change. Correction of the anterior teeth relationships comprised 30% skeletal change and 70% dental change. Conclusion The MEAW technique can produce the desired vertical and sagittal movement of the tooth segment and then effectively stimulate mandibular advancement by utilizing the residual growth potential of the condyle.
文摘Background Many cases of ClassⅡdeformities have been reported to be treated with prefabricated appliances.The aim of this study was to distinguish the clinical effect of traditional custom-made appliances and prefabricated appliances in the treatment of ClassⅡdivision 1 malocclusion.Therefore,soft and hard tissue changes following treatment of ClassⅡdivision 1 malocclusion using the twin-block(TB)appliance was compared to that using the Myofunctional Research Company(MRC)appliance(K1+K2)combined with oral myofunctional treatment(OMT)(MRC+OMT).Methods The study included 22 children(6 boys and 16 girls aged 9–11 years)with ClassⅡdivision 1 malocclusion along with mandibular retrognathism with a 5–12 mm overjet,basic normal maxillary status,and stage 2 or 3 cervical vertebral maturation(CVM).Participants were randomly assigned into two groups,the TB group and the MRC+OMT group for 12 months.Standardized lateral cephalograms were used to assess skeletal,dental,and soft tissue changes from pre-to post-treatment.Independent t-tests were used to compare the initial and final cephalometric status and tissue changes between the groups.Results The TB and MRC+OMT groups resulted in different degrees of lateral changes;however,improvements of skeletal and soft tissue indices were significantly greater in the TB group than in the MRC+OMT group.Conclusion TB was more effective than MRC+OMT in treating children aged 9–11 years with ClassⅡdivision 1 malocclusion.However,further research using custom-made appliances with OMT is recommended,and further investigations are needed to confirm these findings.
基金Supported by Fujian Province Natural Science Foundation,Nos.2016J01437,2017J01260 and 2018J01266the Fujian Medical Innovation Project,No.2015-CX-8+1 种基金the Peking University Cancer Hospital and Institute,Key Laboratory of Carcinogenesis and Translational Research,Ministry of Education/Beijing(2017 Open Project-9)Joint Funds for the innovation of science and Technology,Fujian Province,No.2017Y9074
文摘AIM To assess the long-term prognostic value of vascular endothelial growth factor receptor 1(VEGFR1)and classⅢβ-tubulin(TUBB3)mRNA expression in nonmetastatic rectal cancer.METHODS A total of 75 consecutive patients with non-metastatic rectal cancer from March 2004 to November 2008 were analyzed retrospectively at our institute.The mRNA expressions of VEGFR1 and TUBB3 were detected by multiplex branched DNA liquid-chip technology.The Cutoff Finder application was applied to determine cutoff point of mRNA expression.SPSS software version 22.0was used for analysis.RESULTS The median follow-up was 102.7 mo(range,6-153.6).Theχ~2 and Fisher’s exact tests showed that VEGFR1expression was related to lymph node metastasis(P=0.013),while no relationships between TUBB3 and clinicopathological features were observed.Univariate analysis showed that T stage,lymph node metastasis,tumor differentiation,VEGFR1 and TUBB3 mRNA expression were correlated to overall survival(OS)(P=0.048,P=0.003,P=0.052,P=0.003 and P=0.015,respectively).Also,lymph node metastasis and VEGFR1expression independently influenced OS by multivariate analysis(P=0.027 and P=0.033).VEGFR1 expression was positively correlated with TUBB3(P=0.024).The patients with low expression of both TUBB3 and VEGFR1 presented a better OS(P=0.003).In addition,the receiver operating characteristic analysis suggested that the combination of lymph node metastasis and VEGFR1 had a more favorable prognostic value(P<0.001).CONCLUSION VEGFR1 expression and lymph node metastasis independently and jointly affect survival.Moreover,low expression of VEGFR1 and TUBB3 presented a better OS in patients with non-metastatic rectal cancer,which might serve as a potential prognostic factor.
基金Supported by the Medical Science Research Project Plan of the Hebei Provincial Health Commission,No.20210027.
文摘BACKGROUND The upregulation of serpin family B member 5(SERPINB5)has been linked to the progression of rectal cancer.However,the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.AIM To investigate the roles and mechanisms of SERPINB5 in rectal cancer.METHODS SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis.SW480 cells were transfected with pcDNASERPINB5 or short-hairpin RNA targeting SERPINB5(sh-SERPINB5).Cell proliferation,invasion,and apoptosis were then evaluated.The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1(HSP90AA1)was confirmed through a co-immunoprecipitation assay.Subsequently,pcDNAHSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells,and cell progression was then detected.Moreover,rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression.Additionally,sh-SERPINB5-transfected SW480 cells were implanted into nude mice,and xenograft tumor growth was then evaluated.RESULTS SERPINB5 was prominently upregulated in rectal cancer tissues and cells.SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis.In contrast,SERPINB5 knockdown had the opposite effects.Moreover,SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells.HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis.By contrast,HSP90AA1 knockdown suppressed cell progression.The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression.Additionally,SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.CONCLUSION SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.
