AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric c...AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment.Clinical and pathological information were obtained from the medical records.Gene expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA.Tissue microarrays were constructed from 368 gastric cancer patients.Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity.Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer cases.PKM2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones.Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive cells.Importantly,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION:PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas.Its function and potential as a prognostic marker should be further verified in gastric cancer.展开更多
The transformer-2(tra-2) gene plays a key role in the regulatory hierarchy of sexual differentiation in somatic tissues and in the germline of Drosophila melanogaster.In this study,sequences and expression profiles of...The transformer-2(tra-2) gene plays a key role in the regulatory hierarchy of sexual differentiation in somatic tissues and in the germline of Drosophila melanogaster.In this study,sequences and expression profiles of tra-2 in the Chinese mitten crab Eriocheir sinensis were characterized.Four tra-2 isoforms,designated as Estra-2a,Estra-2b,Estra-2c,and Estra-2d,were isolated.They all contained an RNA-recognition motif(RRM) and a linker region,which shared high similarity with other reported tra-2s.Sequence analysis revealed that Estra-2a,Estra-2b and Estra-2c are encoded by the same genomic locus and are generated by alternative splicing of the pre-mRNA.Compared with the other three isoforms,Estra-2d lacks the RS2 domain.Quantitative real-time PCR showed that all four isoforms were highly expressed in the fertilized egg,and in the 2-4 cell and blastula stages compared with larval stages(P<0.01),suggesting their maternal origin in early embryonic developmental stages.Notably,Estra-2a was highly expressed in male somatic tissues,while Estra-2c was significantly highly expressed in the ovary.These results suggest that Estra-2c is involved in sexual differentiation of the Chinese mitten crab.Our findings provide basic information for further functional studies of the tra-2 gene/protein in this species.展开更多
After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization wi...After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-I infection process begins when the gpl20 subunit of the envelope glycoprotein complex interacts with its receptor（s） on the target cell. The V3 domain of gpl20 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIVol isolates, sequences from the VpU to V3 regions （119 in R5- and 120 X4-tropic viruses; one per patient） were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gpl20v3 signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures （R5-viruses： SI1, E25D; X4-viruses： SllKR, E25KRQ）, other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters： one associated with R5-tropic sequences （bootstrap=0.94）, involving： （a） H13NPv3, E25Dv3, Sllv3, T22Av3 and Q61Hvpu, （b） E25Av3 and L12Fvpu, （c） D44Evpu, R18Qv3 and D80Nvpu; and another associated with X4-tropic sequences （bootstrap=0.97）, involving： （i） E25Iv3 and V10Avpu, （ii） 0-1insVvpc, H13Rv3, I46Lvpc, I30Mv3 and 60-62delvpu, （iii） SllKRv3 and E25KRQv3. Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-I tropism.展开更多
基金Supported by Faculty Research Grant of Yonsei University College of Medicine for 2011,6-2011-0113,6-2011-0146A Faculty Research Grant of Department of Internal Medicine,Yonsei University College of Medicine for 2010Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,Science and Technology,No. 2010-0024248
文摘AIM:To investigate M2 isoform of pyruvate kinase(PKM2) expression in gastric cancers and evaluate its potential as a prognostic biomarker and an anticancer target.METHODS:All tissue samples were derived from gastric cancer patients underwent curative gastrectomy as a primary treatment.Clinical and pathological information were obtained from the medical records.Gene expression microarray data from 60 cancer and 19 noncancer gastric tissues were analyzed to evaluate the expression level of PKM2 mRNA.Tissue microarrays were constructed from 368 gastric cancer patients.Immunohistochemistry was used to measure PKM2 expression and PKM2 positivity of cancer was determined by proportion of PKM2-positive tumor cells and staining intensity.Association between PKM2 expression and the clinicopathological factors was evaluated and the correlation between PKM2 and cancer prognosis was evaluated.RESULTS:PKM2 mRNA levels were increased more than 2-fold in primary gastric cancers compared to adjacent normal tissues from the same patients(log transformed expression level:7.6 ± 0.65 vs 6.3 ± 0.51,P < 0.001).Moreover,differentiated type cancers had significantly higher PKM2 mRNA compared to undifferentiated type cancers(log transformed expression level:7.8 ± 0.70 vs 6.7 ± 0.71,P < 0.001).PKM2 protein was mainly localized in the cytoplasm of primary cancer cells and detected in 144 of 368(39.1%) human gastric cancer cases.PKM2 expression was not related with stage(P = 0.811),but strongly correlated with gastric cancer differentiation(P < 0.001).Differentiated type cancers expressed more PKM2 protein than did the undifferentiated ones.Well differentiated adenocarcinoma showed 63.6% PKM2-positive cells;in contrast,signet-ring cell cancers showed only 17.7% PKM2-positive cells.Importantly,PKM2 expression was correlated with shorter overall survival(P < 0.05) independent of stage only in signet-ring cell cancers.CONCLUSION:PKM2 expression might be an adverse prognostic factor for signet-ring cell carcinomas.Its function and potential as a prognostic marker should be further verified in gastric cancer.
基金Supported by the National High Technology Research and Development Program of China(863 Program)(No.2012AA10A409)the Scientific and Technological Innovation Project of Qingdao National Laboratory for Marine Science and Technology(No.2015ASKJ02)
文摘The transformer-2(tra-2) gene plays a key role in the regulatory hierarchy of sexual differentiation in somatic tissues and in the germline of Drosophila melanogaster.In this study,sequences and expression profiles of tra-2 in the Chinese mitten crab Eriocheir sinensis were characterized.Four tra-2 isoforms,designated as Estra-2a,Estra-2b,Estra-2c,and Estra-2d,were isolated.They all contained an RNA-recognition motif(RRM) and a linker region,which shared high similarity with other reported tra-2s.Sequence analysis revealed that Estra-2a,Estra-2b and Estra-2c are encoded by the same genomic locus and are generated by alternative splicing of the pre-mRNA.Compared with the other three isoforms,Estra-2d lacks the RS2 domain.Quantitative real-time PCR showed that all four isoforms were highly expressed in the fertilized egg,and in the 2-4 cell and blastula stages compared with larval stages(P<0.01),suggesting their maternal origin in early embryonic developmental stages.Notably,Estra-2a was highly expressed in male somatic tissues,while Estra-2c was significantly highly expressed in the ovary.These results suggest that Estra-2c is involved in sexual differentiation of the Chinese mitten crab.Our findings provide basic information for further functional studies of the tra-2 gene/protein in this species.
文摘After infection and integration steps, HIV-1 transcriptions increase sharply and singly-spliced mRNAs are produced. These encode Env （gpl20 and gp41） and auxiliary proteins Vif, Vpr and VpU. The same localization within the unique structure of the mRNAs suggests that the VpU sequence prior to the Env could affect the Env polyprotein expression.The HIV-I infection process begins when the gpl20 subunit of the envelope glycoprotein complex interacts with its receptor（s） on the target cell. The V3 domain of gpl20 is the major determinant of cellular co-receptor binding. According to phenotypic information of HIVol isolates, sequences from the VpU to V3 regions （119 in R5- and 120 X4-tropic viruses; one per patient） were analysed. The binomial correlation phi coefficient was used to assess covariation among VpU and gpl20v3 signatures. Subsequently, average linkage hierarchical agglomerative clustering was performed. Beyond the classical V3 signatures （R5-viruses： SI1, E25D; X4-viruses： SllKR, E25KRQ）, other specific V3 and novel VpU signatures were found to be statistically associated with co-receptor usage. Several statistically significant associations between V3 and VpU mutations were also observed. The dendrogram showed two distinct large clusters： one associated with R5-tropic sequences （bootstrap=0.94）, involving： （a） H13NPv3, E25Dv3, Sllv3, T22Av3 and Q61Hvpu, （b） E25Av3 and L12Fvpu, （c） D44Evpu, R18Qv3 and D80Nvpu; and another associated with X4-tropic sequences （bootstrap=0.97）, involving： （i） E25Iv3 and V10Avpu, （ii） 0-1insVvpc, H13Rv3, I46Lvpc, I30Mv3 and 60-62delvpu, （iii） SllKRv3 and E25KRQv3. Some of these pairs of mutations were encoded always by one specific codon. These data indicate the possible VpU mutational patterns contributing to regulation of HIV-I tropism.
