Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in ca...Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.展开更多
The two-dimensional(2D)C3 N has emerged as a material with promising applications in high performance device owing to its intrinsic bandgap and tunable electronic properties.Although there are several reports about th...The two-dimensional(2D)C3 N has emerged as a material with promising applications in high performance device owing to its intrinsic bandgap and tunable electronic properties.Although there are several reports about the bandgap tuning of C3 N via stacking or forming nanoribbon,bandgap modulation of bilayer C3 N nanoribbons(C3NNRS)with various edge structures is still far from well understood.Here,based on extensive first-principles calculations,we demonstrated the effective bandgap engineering of C3 N by cutting it into hydrogen passivated C3 NNRS and stacking them into bilayer heterostructures.It was found that armchair(AC)C3 NNRS with three types of edge structures are all semiconductors,while only zigzag(ZZ)C3NNRS with edges composed of both C and N atoms(ZZCN/CN)are semiconductors.The bandgaps of all semiconducting C3 NNRS are larger than that of C3 N nanosheet.More interestingly,AC-C3 NNRS with CN/CN edges(AC-CN/CN)possess direct bandgap while ZZ-CN/CN have indirect bandgap.Compared with the monolayer C3 NNR,the bandgaps of bilayer C3NNRS can be greatly modulated via different stacking orders and edge structures,varying from 0.43 eV for ZZ-CN/CN with AB’-stacking to 0.04 eV for AC-CN/CN with AA-stacking.Particularly,transition from direct to indirect bandgap was observed in the bilayer AC-CN/CN heterostructure with AA^stacking,and the indirect-to-direct transition was found in the bilayer ZZ-CN/CN with ABstacking.This work provides insights into the effective bandgap engineering of C3 N and offers a new opportunity for its applications in nano-electronics and optoelectronic devices.展开更多
基金This work was supported by the Natural Science Foundation of China(NSFC 81902577)the Research Foundation for the Postdoctoral Program of Sichuan University(2021SCU12014).
文摘Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer.
基金This work was supported by the National Natural Science Foundation of China(Grant No.21673075).
文摘The two-dimensional(2D)C3 N has emerged as a material with promising applications in high performance device owing to its intrinsic bandgap and tunable electronic properties.Although there are several reports about the bandgap tuning of C3 N via stacking or forming nanoribbon,bandgap modulation of bilayer C3 N nanoribbons(C3NNRS)with various edge structures is still far from well understood.Here,based on extensive first-principles calculations,we demonstrated the effective bandgap engineering of C3 N by cutting it into hydrogen passivated C3 NNRS and stacking them into bilayer heterostructures.It was found that armchair(AC)C3 NNRS with three types of edge structures are all semiconductors,while only zigzag(ZZ)C3NNRS with edges composed of both C and N atoms(ZZCN/CN)are semiconductors.The bandgaps of all semiconducting C3 NNRS are larger than that of C3 N nanosheet.More interestingly,AC-C3 NNRS with CN/CN edges(AC-CN/CN)possess direct bandgap while ZZ-CN/CN have indirect bandgap.Compared with the monolayer C3 NNR,the bandgaps of bilayer C3NNRS can be greatly modulated via different stacking orders and edge structures,varying from 0.43 eV for ZZ-CN/CN with AB’-stacking to 0.04 eV for AC-CN/CN with AA-stacking.Particularly,transition from direct to indirect bandgap was observed in the bilayer AC-CN/CN heterostructure with AA^stacking,and the indirect-to-direct transition was found in the bilayer ZZ-CN/CN with ABstacking.This work provides insights into the effective bandgap engineering of C3 N and offers a new opportunity for its applications in nano-electronics and optoelectronic devices.
